C/EBPß promotes the viability of human bladder cancer cell by contributing to the transcription of bladder cancer specific lncRNA UCA1.

Urothelial Carcinoma Antigen 1 (UCA1) is a cell and tissue specific long non-coding RNA (lncRNA) associated with the tumorigenesis and invasion of bladder cancer. However, the mechanism driving the over-transcription of UCA1 in bladder cancer cells remains unclear. It has been reported that C/EBPß has a significant role of regulation in tumorigenesis. Here we report that the expression of UCA1 was dramatically inhibited in 5637 cells with C/EBPß down-regulation. Additionally, the function tests indicated that C/EBPß could promote 5637 cells growth and colony formation by inducing the expression level of UCA1. These data suggest that C/EBPß was involved in transcriptional regulation of UCA1 and contributed substantially to its high expression and proliferation promoting in bladder cancer cells.

Downregulation of miR-193a-3p inhibits cell growth and migration in renal cell carcinoma by targeting PTEN.

Although miR-193a-3p has been found to be dysregulated in variety of human tumors, little is known about its role in renal cell carcinoma. This study was designed to investigate the function and underlying mechanism of miR-193a-3p in human renal cell carcinoma tissues and cell lines. Here, we demonstrated that the expression of miR-193-3p was increased in renal cell carcinoma tissues and cell lines. In addition, knockdown of miR-193a-3p significantly inhibited cell proliferation and colony formation and induced cells into G1 phase arrest. Meanwhile, the migration potential of 786-O cells was also decreased compared to control group. Furthermore, we identified PTEN as a direct and functional target of miR-193a-3p, at least partly responsible for promoting tumor effect of miR-193a-3p in renal cell carcinoma. Taken together, the findings indicated for the first time that miR-193a-3p functions as a tumor-promoting microRNA by directly targeting PTEN in renal cell carcinoma.

MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3.

PURPOSE: Some microRNA (miRNA) levels have been found to be dysregulated in cancer patients, suggesting the potential usefulness of miRNAs in cancer therapies. The purpose of this study was to investigate the expression of miR-142-5p in human renal cell carcinoma (RCC) and its potential role in tumor growth and metastasis. METHODS: The expression level of miR-142-5p in human RCC tissue and cell lines was determined by quantitative reverse transcription polymerase chain reaction analysis. MTT, colony formation, Transwell, and cell cycle assays were performed to explore the potential functions of miR-142-5p in human RCC cells. The potential target gene of miR-142-5p was identified and confirmed via luciferase reporter assays. RESULTS: miR-142-5p expression was elevated in RCC tissues and cell lines. Overexpression of miR-142-5p significantly promoted cell proliferation and colony formation and could prevent G1 phase arrest among RCC 786-O cells. Meanwhile, the migration potential of 786-O cells was greater than that of control cells. BTG3 was identified as a direct target of miR-142-5p, and re-expression of BTG3 reversed the miR-142-5p-induced cell proliferation. CONCLUSION: miR-142-5p promoted the proliferation and migration of RCC cells by targeting BTG3. With this potential onco-miRNA role in the progression of RCC, miR-142-5p may be a therapeutic target for the treatment of RCC.

PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion.

Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that the PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the -851 to -836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis.

PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation.

Increased expression of pituitary tumor-transforming gene 1 (PTTG1) occurs during mitosis-related sister chromatid segregation, and characterizes various tumor cells, including prostate cancer. Whereas the mechanism remains unclarified. Here, the PTTG1 levels in a prostate cancer cell line, PC3, were modulated by the expression of PTTG1 transgene or shRNA, showing that the PTTG1 levels affected the proliferation of prostate cancer cells, in vitro and in vivo. Moreover, a significant decrease in mothers against decapentaplegic homolog 3 (SMAD3), a key component of transforming growth factor ß (TGFß) signaling pathway, was induced by PTTG1 overexpression. Since SMAD3 is a ubiquitous cell-cycle inhibitor, our data suggest that PTTG1 may promote the proliferation of prostate cancer cells by inhibiting SMAD3-mediated TGFß signaling. To identify a causal link, we expressed SMAD3 in PTTG1-overexpressing PC3 cells and found that SMAD3 expression inhibited the augmented cancer cell proliferation by PTTG1 overexpression. Furthermore, SMAD3 inhibition by short hairpin RNA (ShRNA) completely rescued the cancer cell proliferation in PTTG1 ShRNA-treated PC3 cells. Taken together, our data suggest that PTTG1 promotes the proliferation of prostate cancer cells via the inhibition of SMAD3. SMAD3 thus appears to be a novel therapeutic target for suppressing the growth of prostate cancer.

Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression.

Cell adhesion molecules (CADMs) comprise a protein family whose functions include maintenance of cell polarity and tumor suppression. In this report, we show that the CADM2 gene is repressed in human clear renal cell carcinoma by DNA promoter hypermethylation and/or loss of heterozygosity. Moreover, the loss of CADM2 expression is associated with a higher tumor pathology stage (p<0.05). The re-expression of CADM2 in the renal cancer cell line 786-O significantly suppressed tumor cell growth in vitro and in mouse xenografts by a G1 phase cell cycle arrest and the induction of apoptosis. Lentivirus-mediated CADM2 expression also significantly suppressed cancer cell anchorage-independent growth and invasion. Furthermore, the inhibition of endogenous CADM2 expression using siRNAs induced a tumorigenic phenotype in polarized non-tumorigenic MDCK cells. Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma.

ELL is an HIF-1alpha partner that regulates and responds to hypoxia response in PC3 cells.

BACKGROUND: Eleven-nineteen lysine-rich leukemia (ELL) plays an important role in tumorigenesis and animal development. HIF-1 is a transcriptional factor that functions as a master regulator of O(2) homeostasis. Our previous studies showed that a binding partner of ELL, U19/Eaf2, can modulate HIF-1alpha activity and hypoxia response, suggesting that ELL may also influence HIF-1alpha pathway and hypoxia response. METHODS: Co-localization and co-immunoprecipitation were performed to test the interaction between ELL and HIF-1alpha. PC3 cells with stable ELL knockdown and PC3 cells with stable ELL overexpression, along with their controls, were established using lentiviral expression system. Western blot and real-time PCR were performed to test the effect of ELL on HIF-1alpha protein and its down-stream gene transcription. To elucidate potential effect of hypoxia on ELL, cell growth and colony formation assays were performed using PC3 subline with stable ELL overexpression. RESULTS: ELL is associated with HIF-1alpha in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF-1alpha protein level and down-stream gene expression. As expected, ELL inhibited cell growth and colony formation under normoxia. Interestingly, the inhibition was alleviated under hypoxia. CONCLUSIONS: Our findings suggest that ELL and HIF-1alpha are binding partners and can modulate the functions of each other in hypoxia.

Changes in the androgen levels in the ventral prostate of spontaneously hypertensive rats after castration.

OBJECTIVE: To characterize the changes in androgen levels in the prostate after castration, as androgens are critical in the progression of prostate cancer after castration, but the time at which the androgen remaining in the prostatic cancer tissue after castration exerts its effects is poorly understood. MATERIALS AND METHODS: The ventral prostate (VP) in adult male spontaneously hypertensive rats was excised at 2, 4 and 8 h, 1, 2, 4 and 7 days, and 2, 4 and 8 weeks after castration. The dihydrotestosterone (DHT), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (4-dione) levels in the VP were measured simultaneously using gas chromatography/tandem mass spectrometry. RESULTS: Within 2 days of castration, the DHT and testosterone levels in the VP decreased sharply, while there were no significant changes in the DHEA or 4-dione levels. From 2 days to 2 weeks after castration (2-7 days for 4-dione), there was a sharp peak in tissue androgen levels in the VP (P < 0.05 for all androgens); during the subsequent 6 weeks after castration, all of the tissue DHT, testosterone, DHEA and 4-dione levels gradually increased with time. CONCLUSIONS: These data show the changes which occur in androgen levels in rat VP after castration and support the concept that the adrenal glands compensate for the loss of testicular androgen.

[Pathological changes of benign hyperplastic prostate after removal of innervation of cholinergic pelvic nerve: experiment with spontaneous hypertension rats].

OBJECTIVE: To study the pathological change of benign hyperplastic prostate after removal of the innervation of cholinergic parasympathetic pelvic nerve. METHODS: Sixty-five male spontaneous hypertension rats (SHRs) were randomly assigned into 3 groups: operation group (n = 30) undergoing truncation of bilateral originating branches of parasympathetic pelvic nerve of major pelvic ganglion (MPG) followed by cystostomy, sham operation group (operation control group, n = 30) undergoing cystostomy, and normal control group (n = 5) not undergoing operation. 3, 7, 11, 15 and > or = 21 days after operation 6 rats from the 2 operation groups and 1 from the control group were sacrificed to observe the gross morphology and histological and cellular changes of the prostate glands. RESULTS: The prostate of the operation group on post-operational day 7 showed mild granular solidification and such change progressed gradually over time, the ratio of prostate wet weight/rat body weight was (0.4764 +/- 0.0125) mg/g on day 3, then gradually decreased, and became (0.2749 +/- 0.0197) mg/g > or = 21 days post-operationally; while the ratio of prostate tissue dry weight/wet weight on day 3 was (0.1966 +/- 0.0062), then gradually increased, and became (0.2596 +/- 0.0035) > or = 21 days post-operationally. HE staining showed that the glandular structure gradually became dilated and rounded, with accumulation of prostatic fluid. The glandular epithelial cells showed gradual degeneration, necrosis, and detachment. The glandular epithelium became progressively thinner, the smooth muscles elongated and thinned progressively, and the stromal components showed mild to moderate overgrowth. Electron microscopy showed that the glandular cells gradually underwent vacuolar degeneration and the structures of the basement membrane became fuzzy. The smooth muscle cells degenerated mildly, and the fibroblasts and collagenous fibers in the stroma overgrew slowly. All these histological changes were not found in the sham operation control and normal control groups. CONCLUSION: Remarkable atrophy occurs in benign hyperplastic prostatic gland after radical removal of the innervation of cholinergic parasympathetic pelvic nerve. Such operation may represent a novel therapy for BPH.

[Differential transcription of Bcl-2 and Bax through the cell cycle in prostate cancer cell line].

OBJECTIVE: To investigate the differential expression of apoptosis associated gene Bcl-2 and Bax through cell cycle and its possible clinical meaning. METHODS: The prostate cancer cell line PC-3 was synchronized in M, G1, S and G2 phase using modified thymine deoxyriboside blockage and high pressure N2O technique. The efficiency of synchronization was detected by flow-cytometry. RT-PCR and Western blot methods were used to examine the expression of Bcl-2 and Bax in mRNA and protein level. RESULTS: The synchronized rate of M, G1, S and G2 phase were 92.1%, 87.0%, 80.2% and 75.9% respectively. Bcl-2 was constitutively expressed through the cell cycle, but both the mRNA and protein expression level of Bcl-2 were very high in the G1 phase, dramatically decreased in M, S and G2 phase. The expression level of Bax had no change through the cell cycle. CONCLUSIONS: Cell cycle could influence the expression level of Bcl-2 significantly but not Bax, these might have some clinical relevance.

[Expression of ZNRD1 protein in human renal cell carcinoma].

OBJECTIVE: To investigate the expression of zinc ribbon domain-containing1 (ZNRD1) in human renal cell carcinoma and normal kidney tissues. METHODS: The expression of ZNRD1 protein was examined by immunohistochemical staining in 71 renal cell carcinomas and 24 samples of normal kidney tissue. The correlation between the expressions of ZNRD1 protein and clinicopathologic features was analyzed. The expression of ZNRD1 mRNA and ZNRD1 protein was detected by quantitative reverse transcriptase-polymerase chain reaction (PT-PCR) and Western blot in 20 renal cell carcinomas and corresponding adjacent non-cancerous tissues. RESULTS: ZNRD1 protein was detected mostly in the cell nuclei by immunohistochemistry. The positive expression rate of ZNRD1 protein was 91.7% (22/24) in renal cell carcinomas and 20.8% (5/24) in the normal kidney tissues, with a statistically significant difference between cancer and normal kidney tissue (P < 0.01). However, no significant correlation was observed between ZNRD1 protein expression level and clinicopathologic features (P > 0.05). ZNRD1 mRNA expression level was significantly higher in renal cell carcinomas (0.6186) than that in the normal kidney tissues (0.4273) assessed by RT-PCR (P < 0.01). The expression level of ZNRD1 protein by Western blot was 0.5623 in renal cell carcinomas, significantly higher than that in normal kidney tissues (0.3885, P < 0.01). CONCLUSION: ZNRD1 gene and ZNRD1 protein may play an important role in the carcinogenesis of renal cell carcinoma. Further investigation is still needed.

The important anti-apoptotic role and its regulation mechanism of PTTG1 in UV-induced apoptosis.

Pituitary tumor transforming gene (PTTG1) is widely detected in many tumors. Increasing evidence reveals that PTTG1 is associated with cell proliferation, cellular transformation and apoptosis. However, the functions of PTTG1, especially its role in DNA damage-induced apoptosis, remain largely unclear. In this report, we used UV irradiation to induce apoptosis in HeLa cells to examine the role of PTTG1 in UV-induced apoptosis by RNAi-mediated knockdown and overexpression of PTTG1. RNAi-mediated knockdown of PTTG1 expression increased and overexpression of PTTG1 decreased the UV-induced apoptosis. Furthermore, UV irradiation decreased PTTG1 mRNA and protein expression. These effects were found to be mediated by JNK pathway. Therefore, PTTG1 had an important anti-apoptotic role in UV-induced apoptosis and this role was mediated by JNK pathway. These results may provide important information for understanding the exact role and the regulation mechanism of PTTG1 in UV-induced apoptosis.

[The pathological change of rats' benign hyperplastic prostate after radical denervation].

OBJECTIVE: To study the pathological change of rats' benign hyperplastic prostate (BHP) after radical denervation. METHODS: A total of 65 male spontaneous hypertension rats (SHR) at 30 weeks age were randomly assigned into treatment group, sham surgery control group and normal control group. In surgery group, all the axonal branches of the major pelvic ganglion (MPG) supplying the bilateral prostate were truncated, followed performing of cystostomy; In sham surgery control group, only cystostomy was performed; In normal control group, no procedure was performed. The rats were sacrificed at 3, 7, 11, 15 and >or= 21 d post-operation respectively. The gross morphological changes of prostate in all animals were observed. RESULTS: In treatment group, the prostate in 3 d post-operation showed granular solidification and shrunken volume and the changes occurred gradually over time. The glandular epithelial cells showed gradual degeneration, necrosis and detachment. The glandular epithelium became progressively thinner, the smooth muscles elongated and thinned progressively and the stromal components showed mild to moderate overgrowth. At the later stage, the glandular epithelium, glandular lumen and smooth muscles gradually disappeared and the prostate was largely replaced by connective tissues. Electron microscopic study showed that the glandular cells gradually underwent vacuolar degeneration and the structures of basement membrane became fuzzy. The smooth muscles cells degenerated overtime and the fibroblasts and collagenous fibers in the stroma overgrew slowly. At the late stage, most of the glandular cells became necrotic, the basal membrane and smooth muscle cells disappeared and collagenous fibers were highly hyperplasic. In surgery group in 3 d post-operation, the S-100 staining of nerve fiber was diffuse and disappeared after 11 d while it persisted normally in other groups. The two values in sham surgery control group showed no significant changes post-operatively. CONCLUSIONS: After radical denervation, the rat prostate with benign hyperplasia (gland and smooth muscles) undergoes dramatic atrophic changes and the volume decreases significantly. It suggests that this treatment may represent a novel therapy for BPH.

Significance of TWIST expression and its association with E-cadherin in bladder cancer.

Recently, TWIST, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of human cancer. The aim of this study was to investigate the significance of TWIST expression in bladder cancer using tissue microassays generated from 226 bladder tissue specimens. Using immunohistochemical staining, we studied TWIST expression levels in nonmalignant bladder tissues (n = 37), primary bladder cancer tissues (n = 164), and 25 cases of matched lymph node metastatic lesions. The association between TWIST expression levels and tumor staging and grading, as well as metastatic potential, was analyzed by statistical analysis. Our results showed that TWIST protein expression was significantly higher in bladder cancer specimens compared with nonmalignant tissues (P < .001), indicating its positive role in the development of bladder cancer. In addition, increased TWIST expression levels were associated with advanced-stage and high-grade tumors, suggesting its involvement in the progression of this cancer. Furthermore, TWIST expression was much higher in the metastatic lesion compared with its primary site (P < .05). More importantly, the increased TWIST expression in bladder cancer specimens was correlated with decreased membranous expression of E-cadherin, a cell adhesion molecule that plays a key role in the metastatic progression of human cancer. Our results demonstrate TWIST as a novel positive factor in the development and progression of bladder cancer and suggest a marker for advanced bladder cancer.

Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma.

Epigenetic mechanisms involving DNA methylation and chromatin remodeling are important in silencing tumor suppressor genes (TSG) in various malignancies, including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1 promoter with resultant gene silencing has been reported in several tumors, but not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the corresponding non-malignant tissues, and the correlation of DLC1 methylation with the clinicopathological characteristics of RCC patients. Although DLC1 methylation and downregulation were only detected in one of seven RCC cell lines using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC tumors, which was further confirmed by direct sequencing of MSP products and high-resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non-malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared to be a relatively early event during renal tumorigenesis since 33% of the RCC tumors with pT1 (TNM staging) showed methylation, which is similar to other late stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a subset of RCC tumors and may play a role in renal carcinogenesis.

Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma.

PURPOSE: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. EXPERIMENTAL DESIGN: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. RESULTS: UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. CONCLUSIONS: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

The leader sequence triggers and enhances several functions of clusterin and is instrumental in the progression of human prostate cancer in vivo and in vitro.

OBJECTIVE: To investigate the role of the leader sequence (which during clusterin biosynthesis facilitates its proper post-translational processing and secretion) in the functional activities of clusterin, a ubiquitous secretory glycoprotein with many biological functions, reported to be pro-apoptotic and anti-apoptotic in target cells, but for which the dual mechanism remains unclear. MATERIALS AND METHODS: We designed an expression vector starting from the second in-frame ATG on the full-length human clusterin cDNA that was capable of driving the expression of both the full-length and the truncated isoforms of clusterin. We established stable expression clones of the androgen-dependent prostate cancer line LNCaP expressing clusterin with and without the leader sequence. This induced expression provided an opportunity to evaluate both the in vivo and in vitro actions of clusterin expression. RESULTS: The LNCaP cells expressing clusterin with the leader sequence resisted apoptosis induced by tumour necrosis factor (TNF)-alpha, but clones with no leader sequence were highly susceptible to TNF-alpha-induced apoptosis. Furthermore, in the absence of the leader sequence, the expressed clusterin had a molecular weight consistent with that of the predicted holoprotein (40 kDa), suggesting a compromised post-translational processing with diffuse distribution throughout the cytoplasm. However, cells transfected with the full-length vector expressed clusterin of 60 and 35 kDa variants, and located exclusively in the Golgi apparatus. In vivo, only the overexpression of the full-length clusterin is anti-apoptotic and stimulates the proliferation of tumour. CONCLUSION: The leader sequence is important in determining the functions of clusterin, which include anti-apoptotic and anti-necrotic properties. The lack of the leader sequence allowed the incompletely processed clusterin to induce apoptosis in target cells; without the leader sequence, clusterin functions differently. Thus, the leader sequence is a trigger for many functions of clusterin in the progression of human prostate cancer cells.

[Expression of hypoxia-inducible factor-1-alpha, hypoxia-inducible factor-2alpha and vascular endothelial growth factor in sporadic clear cell renal cell renal cell carcinoma and their significance in the pathogenesis thereof].

OBJECTIVE: To investigate the expression of hypoxia-inducible factor (HIF)-1-alpha, HIF-2alpha, and vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and to analyze the relationship among them. METHODS: Samples of CCRCC were obtained from 107 patients during resection. Immunohistochemistry was used to detect the expression of HIF-1-alpha, HIF-2alpha, and VEGF in the tumor tissues and normal kidney tissues distant from the tumor. The microvessel density (MVD) was observed by microscopy. RESULTS: HIF-1-alpha and HIF-2alpha were not expressed in the normal kidney tissues. However, in the tumor tissues the HIF-1-alpha positive rate was 69.2% (74/107), significantly lower than that of the HIF-2-alpha (80.5%, 88/107, P = 0.001), the VEGF positive rate was 78.5% (84/107). The VEGF positive rate of the HIF-1-alpha-positive group was 90.5%, significantly higher than that of the HIF-1-alpha-negative group (51.5%, P = 0.001). The VEGF positive rate of the HIF-2-alpha-positive group was 89.8%, significantly higher than that of the HIF-1-alpha-negative group (26.3%, P = 0.001). The MVD of the 64 HIF-1alpha, HIF-2alpha, and VEGF positive samples was 697, significantly higher than that of the 13 HIF-1alpha, HIF-2alpha, and VEGF negative samples (391, P = 0.001). The MVD of the HIF-2alpha positive samples was 678 +/- 324, significantly higher than that of the HIF-2alpha negative samples (383 +/- 293, P = 0.001). The MVD of the VEGF positive samples was 692 +/- 325, significantly higher than that of the VEGF negative samples (384 +/- 269, P = 0.001). Spearman correlation analysis showed that MVD was strongly positively correlated with HIF-2alpha and VEGF. Mann-Whitney U test showed that HIF-1alpha and HIF-2alpha were not correlated with the staging of CCRCC. CONCLUSION: HIF-2alpha is expressed more frequently in sporadic CCRCC than HIF-1alpha. Both HIF-1alpha and HIF-2alpha upregulate the VEGF expression and angiogenesis, especially HIF-2alpha.

[The study of relationship between nuclear metrix protein 22 urinary level and the grade and stage of bladder transitional cell carcinoma].

OBJECTIVE: To assess the relationship between nuclear matrix protein (NMP) 22 urinary level and the grade and stage of bladder transitional cell carcinoma. METHODS: From June 1999 to March 2005 642 patients underwent NMP22 test, and then the test by cystoscope and pathology were performed in 1 week to 1 month. According to the pathological grade, the patients were divided into 3 groups: group G(1): 69 cases, male 58 and female 11; group G(2): 375 cases, male 255 and female 120; group G(3): 198 cases, male 143 and female 55. And the difference of NMP22 between each group were compared. Meanwhile, according to pathological stage, 239 patients were divided into 3 groups: group PT(1): 121 cases, male 76 and female 45; group PT(2): 65 cases, male 37 and female 28; group PT(3): 53 cases, male 29 and female 24. And the difference of NMP22 between each group were compared. RESULTS: The concentrations of NMP22 had significant difference between the 3 groups which divided according to pathological grade (Kruskal-Wallis test chi(2) = 67.547, P < 0.001); The concentrations of NMP22 had significant difference between the 3 groups which divided according to pathological stage (Kruskal-Wallis test chi(2) = 20.629, P < 0.001). CONCLUSIONS: There is a relation between NMP22 urinary level and the grade and stage of bladder transitional cell carcinoma.

Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer.

Recently, the pituitary tumor transforming gene 1 (PTTG1) has been suggested to be an oncogene. To investigate whether PTTG1 plays a positive role in the pathogenesis of prostate cancer, PTTG1 protein expression was examined in prostate tissue samples by immunohistochemistry. PTTG1 expression was detected in a high percentage of prostate cancer tissues (34/41, 82.9%), but to a much lesser extent in non-malignant tissues (5/14, 35.7%). To further confirm these results, the expression vectors containing either the PTTG1 or antisense-PTTG1 gene were transfected into a prostate cancer cell line, LNCaP, and the cell proliferation rate was studied, as well as tumorigenicity in the LNCaP cells expressing different levels of the PTTG1 protein. Ectopic PTTG1 gene expression promoted prostate cancer cell proliferation and tumorigenesis both in vitro and in nude mice. In contrast, down-regulation of PTTG1 led to suppression of tumor cell growth. These results suggest that PTTG1 may be a potential prognostic marker for prostate cancer and that the down-regulation of PTTG1 may be a therapeutic target in the suppression of prostate cancer growth.