ABSTRACT
OBJECTIVE: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. METHODS: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. RESULTS: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP- 9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). CONCLUSIONS: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.
Subject(s)
Cell Movement , Cell Proliferation , Chemokine CXCL12/metabolism , Pancreatic Neoplasms/pathology , Receptors, CXCR4/metabolism , Apoptosis , Blotting, Western , Cell Adhesion , Chemokine CXCL12/genetics , Humans , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptors, CXCR4/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Urokinase-Type Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/metabolismABSTRACT
Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.
Subject(s)
Lung Neoplasms/genetics , Polymorphism, Genetic/genetics , Receptors, Nicotinic/genetics , Case-Control Studies , China , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm StagingABSTRACT
Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.
Subject(s)
Female , Humans , Male , Middle Aged , Lung Neoplasms/genetics , Polymorphism, Genetic/genetics , Receptors, Nicotinic/genetics , Case-Control Studies , China , Gene Frequency , Genetic Predisposition to Disease , Genotype , Lung Neoplasms/pathology , Neoplasm StagingABSTRACT
OBJECTIVE: To investigate the expression of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue and relationship with progression of breast carcinoma. METHODS: 92 cases of breast carcinoma tissue and homologous paraneoplastic breast tissue were selected, expressive level of HER-2/neu mRNA and RECK mRNA were detected with RT-PCR, expressive difference of HER-2/neu mRNA and RECK mRNA were contrasted between breast carcinoma tissue and homologous paraneoplastic breast tissue, along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma. RESULTS: The level of HER-2/neu mRNA was higher and RECK mRNA was lower in breast carcinoma tissue than homologous paraneoplastic breast tissue, the expressive level of HER-2/neu mRNA and RECK mRNA was remarkably different along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma, there was a negative correlation between expressive level of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue. CONCLUSIONS: Expression of HER-2/neu mRNA and RECK mRNA was abnormal in breast carcinoma tissue, HER-2/neu mRNA and RECK mRNA regulate each other and mutual participate occurrence and progression of breast carcinoma.
Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , GPI-Linked Proteins/genetics , Gene Expression Regulation, Neoplastic , Receptor, ErbB-2/genetics , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma/metabolism , Carcinoma/pathology , Female , GPI-Linked Proteins/metabolism , Humans , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Both environmental and genetic factors participate in the pathogenesis of lung cancer. The aim of this study was to explore the association between CHRNA3 polymorphisms of the nicotinic acetylcholine receptor gene and lung cancer risk in a hospital-based, case-controlled study. Single nucleotide polymorphisms (SNPs) in CHRNA3 rs3743073 (A>G) were determined using the TaqMan-MGB probe technique in 600 lung cancer cases and 600 normal controls. The differences in genotype and allele frequency were compared between groups and their association with lung cancer. The genotype frequency of rs3743073 (A>G) demonstrated Hardy-Weinberg equilibrium (P<0.05). The genotype and allele frequencies were significantly different between the cancer and control groups (P<0.05). Compared with patients with the TT genotype, lung cancer incidence was increased in patients with the TG and GG genotypes (OR=1.68; 95% CI, 1.30-2.19; P<0.05; OR=1.30; 95% CI, 1.05-1.61; P<0.05, respectively). Patients with rs3743073G variant alleles (TG and GG) were at greater risk (OR=0.65; 95% CI, 0.50-0.84; P<0.05) of developing lung cancer. Increased risk associated with rs3743073G variant alleles was observed in male smokers over the age of 60 (P<0.05). In this cohort, the CHRNA3 gene rs3743073G variant genotype significantly increased lung cancer risk, especially in male smokers over the age of 60.
Subject(s)
Lung Neoplasms/genetics , Polymorphism, Single Nucleotide , Receptors, Nicotinic/genetics , Age Factors , Aged , Alleles , Case-Control Studies , Cohort Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Incidence , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Male , Middle Aged , Odds Ratio , Risk Factors , Sex Factors , SmokingABSTRACT
OBJECTIVE: To examine the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in gastric carcinoma, and investigate its clinical significance, at the same time analyze the correlation between MT1-MMP and RECK expression. METHODS: MT1-MMP and RECK expression in surgically resected tissue samples of gastric carcinoma was examined by immunohistochemical method (two-step method) , and its correlation with clinicopathological factors was analyzed. RESULTS: Among the 44 gastric carcinoma samples, 37 (84.1%) were stained positive for MT1-MMP, and 31 (70.5%) for RECK. The expression of MT1-MMP was much higher in poorly differentiated gastric carcinoma samples than moderately and well-differentiated samples (P = 0.015). The expression level of MT1-MMP was associated with invasive depth of tumor cells (P = 0.007), but no difference between sex and lymph node metastasis. On the contrary, the well-differentiated samples showed higher expression of RECK than poorly and moderately differentiated gastric carcinoma samples (P = 0.006). The expression level of RECK did not correlate with sex, lymph node metastasis and invasive depth of tumor cells. RECK expression showed no relation to MT1-MMP expression in the gastric carcinoma. CONCLUSION: Overexpression of MT1-MMP in gastric carcinoma may play an important role during tumor differentiation and metastasis, the RECK protein may have positive effects on the tumor differentiation.
