No Association between ABCB1 G2677T/A or C3435T Polymorphisms and Survival of Breast Cancer Patients-A 10-Year Follow-Up Study in the Polish Population.

Many intensive studies are devoted to identifying novel cancer diagnostics or therapy strategies that would boost cancer therapy efficacy and recovery rates. Importantly, polymorphisms in the genes coding for ABC family proteins were considered good candidates for cancer development risk or cancer drug resistance markers. For this reason, we decided to assess the contribution of ABCB1's most common variants (i.e., G2677T/A in exon 21/rs2032582 and C3435T in exon 26/rs1045642) to the cancer therapy response in breast cancer patients. A 10-year follow-up analysis of 157 breast cancer patients was performed. Clinical assessment, ABCB1 polymorphism status, estrogen/progesterone/human epidermal receptors status, and other characteristics were compared according to the follow-up status using the Chi-square statistic. For the analysis of overall survival curves in TCGA breast cancer patients, the Xena browser was used. We show that neither 2677 nor 3435 polymorphisms contributed to the survival of breast cancer patients. Interestingly, but not surprisingly, estrogen and progesterone receptors status were good prognostic factors and positively correlated with a disease-free survival for up to 10 years. To summarize, ABCB1 polymorphisms status may be one of the numerous factors that affect cancer development. However, they may not be the critical ones when it comes to risk or recovery assessment. Consequently, they may not be treated as reliable prognostic or predictive markers in breast cancer patients' evaluation, which supports the previous findings and current knowledge.

LEP (-2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population.

On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. The study involved 209 women aged 59.6 ± 11 years diagnosed with breast cancer and 202 healthy women aged 57.8 ± 8.2 years, who were blood donors. Polymorphism were evaluated by PCR-RFLP reaction followed by the verification of part of the samples by sequencing. The results of the study confirmed obesity as a significant breast cancer development risk factor in Polish women. However, no significant association between the studied polymorphisms and breast cancer risk or severity of the neoplastic disease was found. Interestingly, it was shown that wild type 223Gln>Gln leptin receptor (LEPR) was statistically more common in women with human epidermal growth factor receptor 2 negative (HER2-) than human epidermal groth factor receptor 2 positive (HER2+) breast cancer and wild type form of 2548G>A LEP was more common in women with progesterone receptor positive (PR+) than progesterone receptor negative (PR-) breast cancer. Studied polymorphisms of the LEP and LEPR genes do not increase breast cancer risk in the population of Polish women. However, they can affect PR an HER receptors expression and thus the severity of the disease. Noteworthy, this interesting correlation is being reported for the first time and might constitute an essential contribution to the identification of molecular mechanisms of carcinogenesis.

The non-canonical functions of telomerase: to turn off or not to turn off.

Telomerase is perceived as an immortality enzyme that enables passing the Hayflick limit. Its main function is telomere restoration but only in a limited group of cells, including cancer cells. Since it is found in a vast majority of cancer cells, it became a natural target for cancer therapy. However, it has much more functions than just altering the metabolism of telomeres-it also reveals numerous so-called non-canonical functions. Thus, a question arises whether it is always beneficial to turn it off when planning a cancer strategy and considering potential side effects? The purpose of this review is to discuss some of the recent discoveries about telomere-independent functions of telomerase in the context of cancer therapy and potential side effects.

Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer.

Telomere shortening is associated with cancer development, primarily through the induction of genomic instability. The majority of studies have indicated that individuals with shorter blood telomeres may be at a higher risk of developing various types of cancer. There is increasing evidence that the study of the alterations in telomere length may improve cancer prognosis. The aim of the present study was to verify the use of telomere length parameters in the diagnostics of breast cancer stage. Telomere length was analyzed in the blood leukocytes of 52 patients with breast cancer relative to 47 control subjects using quantitative polymerase chain reaction. The effects of stage, grade, estrogen receptor, progesterone receptor and human epidermal growth factor 2 (HER2) status were assessed. The current study demonstrated that the average telomeric sequence length was significantly shorter in leukocytes from individuals diagnosed with a more severe stage of breast cancer (T2N1M0) than in leukocytes in the early stages of the disease (T1N0M0) (P=0.0207). Furthermore, the data indicated that telomeres in leukocytes derived from patients with HER2+ breast cancer were significantly longer compared with those with the HER2- type (P=0.0347). These results suggest that the assessment of telomeres in blood leukocytes may, at least partially, correspond with breast cancer staging and HER2 receptor status.

Relative levels of let-7a, miR-17, miR-27b, miR-125a, miR-125b and miR-206 as potential molecular markers to evaluate grade, receptor status and molecular type in breast cancer.

MicroRNAs (miRNAs/miRs) are a class of short, single­stranded nucleic acids, which have been investigated as potential molecular markers for various types of cancer. The gold­standard and most sensitive method for comparing miRNA levels in cancer tissues is reverse transcription­quantitative polymerase chain reaction (RT­qPCR). This technique uses stably expressed genes for normalisation. The aim of the present study was to improve this model of analysis in the context of RT­qPCR results. A total of six known miRNAs (let­7a, miR­17, miR­27b, miR­125a, miR­125b and miR­206), RNU6B RNA and five mRNAs [erb­b2 receptor tyrosine kinase 2 (ERBB2), hydroxymethylbilane synthase and polymerase (RNA) II (DNA directed) polypeptide A] were analysed pair­wise, in order to determine which biomarker pairs best correlated with the histological groups of 27 breast cancer samples. The lowest P­values and the highest area under the curve values in the receiver operating characteristic analysis were used to select the optimum ratios for discrimination among groups. Among the 21 pairs, miR­17/miR­27b and miR­125a/RNU6B best discriminated three groups of samples with different tumour grades (G classification). miR­125b/miR­206 best discriminated two groups of samples with different tumour sizes (pT), let­7a/RNU6B best discriminated two groups of samples with different lymph node status (pN), and let­7a/miR­125b best discriminated groups of samples with negative and positive oestrogen and progesterone receptor status. No pair of miRNAs was found to discriminate well between groups with either a negative or positive human epidermal growth factor receptor 2 (HER2) status. However, one miRNA/mRNA pair, miR­125a/ERBB2, discriminated HER2­negative from HER2­positive groups. The breast cancer samples investigated in the present study were grouped by immunohistological methods into three molecular classes: Luminal, HER2 positive and basal (L, H and B, respectively). In order to discern L from H and L from B, two miRNA pairs were selected: miR­125a/miR­125b and miR­125a/miR­206. In conclusion, the pair­wise method of RT­qPCR data analysis may be a reasonable alternative to the standard method of using stably expressed reference genes, such as RNU6B RNA, for normalisation. This method may increase the classification power of miRNA biomarkers in breast cancer diagnostics.

Health behaviours among women diagnosed with breast tumours.

UNLABELLED: Breast cancer (BC) is one of the most common neoplasms and the second biggest cause of death among women. The aim of the study was to investigate how separate risk factors influence the development of breast neoplasms. MATERIALS AND METHODS: The study included 200 women aged between 17 and 86 years diagnosed with breast neoplasm, who were treated at the Department of Oncological Surgery in Poznan. The study included patients who underwent an operation because of a benign or malignant breast tumor. The questionnaire was completed according to the patients' answers. The histopatological diagnosis was taken from their medical history with the patients'prior consent. The statistical analysis was performed using the Statistica programme at the Department of Computer Science and Statistics of the Poznan University of Medical Sciences. The study was accepted by the Bioethics Commission of the University. RESULTS: The correlation between working status, menopausal age, being overweight, obesity, arterial hypertension, smoking, and whether BC was observed at present or in the past. Smoking was also related to a two-fold increase in malignant cancer (OR = 1.97). A BMI above 24.5 kg/m2 was associated with a nearly three-fold increase in BC (OR = 2.61). CONCLUSIONS: The results of the study offer very important implications because some of the factors which correlated positively with BC can be modified. We may postulate that a modification to the lifestyle in the sense of giving up smoking and a well-balanced diet combined with physical activity, leading to normal weight being maintained, could have a positive effect in decreasing BC development.

The clinical usefulness of assessing the concentration of cell adhesion molecules sVCAM-1 and sICAM-1 in the serum of women with primary breast cancer.

AIM OF THE STUDY: Assessment of the concentrations of the soluble forms of the cell adhesion molecules sVCAM-1 and sICAM-1 in serum of female breast cancer patients. These concentrations were assessed in relation to factors such as: age, clinical stage of disease, histological grade of malignancy, the status of the local axillary lymph nodes, and the size of the primary tumour. MATERIAL AND METHODS: A total of 103 patients with primary breast cancer, aged 29 to 89 years, were investigated. The control group consisted of 40 healthy women. The concentration of sVCAM-1 and sICAM-1 was assessed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of the study suggest that the level of sVCAM-1 and sICAM-1 in the serum of women with breast cancer was significantly higher than that seen in the serum of healthy women. A relationship between the level of adhesion molecules and the stage of clinical disease advancement was discovered. There was a correlation between the increasing concentrations of sVCAM-1 and sICAM-1 and with the aggressiveness of the disease. Significant differences were also found in the group of women with metastases to the axillary lymph nodes and women with no metastasis. Similar correlations were found between sVCAM-1 and sICAM-1 levels and the size of primary tumour. CONCLUSIONS: The results obtained suggest that the assessment of the soluble forms of sVCAM-1 and sICAM-1 may be useful indicators in the assessment of the clinical advancement of breast cancer.

Clinical usefulness of assessing VEGF and soluble receptors sVEGFR-1 and sVEGFR-2 in women with breast cancer.

INTRODUCTION: The biological activity of VEGF depends on the presence of its specific receptors on the endothelial surface: VEGFR-1, VEGFR-2, and on their soluble forms sVEGFR-1 and sVEGFR-2. The binding of the membrane-bound receptors with VEGF affects the permeability, proliferation and migration of vascular endothelial cells. This creates the necessary conditions for the vascularisation of solid tumours and for the spread of remote metastases. The sVEGFR-1 and sVEGFR-2 receptors are believed to be natural inhibitors of VEGF. OBJECTIVE: To determine the clinical usefulness of VEGF and the sVEGFR-1 and sVEGFR-2 receptors level assay in women with primary breast cancer. The assessment also took into account: patient's age, stage of the disease, histological grade, status of the axillary lymph nodes and size of the primary tumour. MATERIAL AND METHODS: The concentrations of VEGF, sVEGFR-1 and sVEGFR-2 were ascertained in 103 women with primary breast cancer. The concentrations of VEGF in the plasma, and those of the soluble receptors sVEGFR-1 and sVEGFR-2 in the serum, were assessed by ELISA, R&D Systems. RESULTS: The study found significantly raised concentrations of VEGF, sVEGFR-1 and sVEGFR-2 in the serum of women with breast cancer, relative to the values obtained from the control group. It was found that with increasing clinical stages of the disease, the levels of VEGF and concentrations of sVEGFR-1 and sVEGFR-2 also increased. Similar findings were noted when assessing the degree of the histological grade of the tumours. Significantly higher values of VEGF protein and the assessed receptors were obtained from women with metastases to the axillary lymph nodes. A positive relationship, though without statistical significance, was noted between the concentration of sVEGFR-2 and the size of the tumour. CONCLUSIONS: The high concentrations of the VEGF cytokine and the sVEGFR-1 and sVEGFR-2 receptors in women with breast cancer are responsible for giving rise to the processes of tumour angiogenesis. The concentrations of the VEGF protein and the soluble forms of the receptors sVEGFR-1 and sVEGFR-2 in the serum of breast cancer patients showed positive correlations with the clinical stage of the disease. These results point to the usefulness of VEGF assessment and its soluble receptors in the clinical evaluation of patients with breast cancer.

rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients.

Expression of MIR125A is diminished in breast tumors, however the reason for the hsa-mir-125a decrease in the cancer is not known. HER2 is encoded by ERBB2, a target for hsa-miR-125a which interacts with the 3'UTR of ERBB2 mRNA. The present study reveals that a polymorphism (rs12976445) within the pri-miR-125a sequence correlates with the amount of mature hsa-miR-125a in breast tumor samples. miRNA, RNA and DNA were extracted from breast cancer samples obtained from 26 patients. Following immunohistological evaluation of the samples, the ERBB2, PGR and ESR1 mRNA profiles were also analyzed using real-time PCR. Genomic DNA was sequenced using MIR125A flanking primers. PCR products were analyzed using a BaeGI restriction enzyme specific to the rs12976445 variant. The rs12976445 variant (C/T and C/C) correlated with a lower level of hsa-miR-125a in comparison with the T/T variant. The expression of HER2 mRNA was increased in tumors with the rs12976445 variant (C/T and C/C) compared with T/T. We conclude that rs12976445 may be a potential prognostic marker of HER2 expression in breast cancer. Its predictive value on the efficacy of trastuzumab treatment in patients with HER2-positive breast cancer warrants further study.

Murine double minute clone 2,309T/G and 285G/C promoter single nucleotide polymorphism as a risk factor for breast cancer: a Polish experience.

BACKGROUND: Breast cancer is a multifactorial disease caused by complex interactions between genetic and environmental factors. Recently, a functional polymorphism, MDM2 285G>C (rs117039649), has been discovered. This polymorphism antagonizes the effect of the 309T>G (rs2279744) polymorphism on the same gene, resulting in decreased MDM2 transcription. METHODS: The MDM2 285G>C and 309T>G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis in women with breast cancer (n=468) and controls (n=550). RESULTS: The odds ratio (OR) for breast cancer patients with the MDM2 285C/C and 285G/C genotypes was 0.4768 (95% confidence interval [CI] 0.2906-0.7824; p=0.0033, pcorr=0.0066). We also found a significantly lower frequency of the MDM2 285C allele in patients with breast cancer than in controls: the OR for the C allele in patients with breast cancer was 0.4930 (95% CI=0.3059-0.7947, p=0.0031, pcorr=0.0062). The p value of the chi-square test for the trend observed for the MDM2 285G>C polymorphism was statistically significant (ptrend=0.0036). The statistical power of this study amounted to 85% for the G/C or C/C genotypes and 85% for the C allele. However, we did not observe significant differences between the distribution of MDM2 309T>G genotypes and alleles in patients with breast cancer and healthy controls. CONCLUSION: In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer.

Study of ABCB1 polymorphism frequency in breast cancer patients from Poland.

BACKGROUND: The accumulation of mutagenic substances in the human body may result in DNA metabolism disruption followed by carcinogenesis. As a consequence of mutations in the genes coding for transmembrane protein pumps, the intracellular concentration of xenobiotics may significantly increase. This, in turn, may provoke altered risk for cancer development. The gene known to be the most relevant in the transport of numerous compounds is ABCB1 (also known as MDR1). Numerous mutations and polymorphisms that affect the encoded protein's (PgP) function were identified in this gene. The aim of the study was to define the frequency of 2677G>A,T and 3435C>T polymorphisms in a population of Polish breast cancer patients and to estimate their contribution to cancer development. METHODS: The polymorphism frequency analysis (209 patients vs. 202 control subjects) was performed either by allele-specific amplification (2677G>A,T) or by restriction fragment length polymorphism (RFLP) using the SAU3AI restriction enzyme (3435C>T) followed by verification with hybridization probe assays in a Real-Time system and sequencing. RESULTS: In the control group the frequency of individual 2677 genotypes was: wild homozygous GG = 34%, heterozygous G/T or G/A = 52.5% and variant homozygous AA or TT = 13.5%, while the genotype frequency in the group of studied patients was 43.5, 44.5 and 12%, respectively. In the control group, the frequency of individual 3435 genotypes was: CC = 25.4%, CT = 50.2%, TT = 24.4%, while the genotype frequency in the group of studied patients was 23, 46 and 31%, respectively. CONCLUSION: Thus, no significant differences in the studied polymorphism frequencies were observed. It is then suggested that the studied polymorphisms, although probably good candidates in other tissue cancer types, might not be good predictive factors in breast cancer risk or development in Caucasians.

[Analysis of the odds ratio for developing breast cancer in women]. / Analiza ilorazu szans zachorowania na nowotwory zlosliwe gruczolu piersiowego kobiet.

Malignant breast cancer is the most common neoplasm in women in most developed countries. The majority of cases of breast cancer are probably connected with environmental factors and lifestyle. According to the current state of knowledge, modification of risk factors may contribute to the reduction of breast cancer cases and individual assessment performed by selecting a group of women with increased risk may help to reduce mortality. The purpose of the study was to analyze risk factors affecting the increase of odds ratio (OR) for developing breast cancer and to define in which range OR increases or decreases significantly. The participants of the study were healthy women with no changes in mammary glands and women with breast cancer diagnosed on the basis of histopathological examination. The study was carried out in Great Poland and Lubuskie province between 2005 and 2006. The total number of participants was 371 females, aged 35-70 years. The highest risk of breast cancer was observed in women over 55, BMI > 30, who had > 5 deliveries, with cancer family history and suffering from severe depression. Apart from cancer family history all other factors are potentially modifiable. Appropriate education of women can result in reduction of breast cancer risk.

CCL2 -2518 A/G single nucleotide polymorphism as a risk factor for breast cancer.

The contribution of the CCL2 -2518 A>G (rs 1024611) polymorphism in the occurrence and progression of various cancers has been found to be discordant. We studied the prevalence of the CCL2 -2518 A>G polymorphism in patients with breast cancer (n = 160) and controls (n = 323) in a sample of the Polish population. There were no significant differences in CCL2 -2518 A>G genotypes between patients with breast tumors and controls. Odds ratio (OR) for patients bearing the GG genotype was 1.481 (95% CI = 0.7711-2.845, P = 0.2358), and OR of the GG and AG genotypes was 0.7269 (95% CI = 0.4967-1.064, P = 0.1002). There was also no significant distinction in the prevalence of alleles between patients and healthy individuals. OR for the CCL2 -2518 G allele frequency was 0.8903 (95% CI = 0.6611-1.199, P = 0.4441). Analysis of the association between tumor size, lymph node metastases, histological grade, and distribution of genotypes and alleles for the CCL2 -2518 A>G polymorphism also did not show significant differences. Our results did not show association of the CCL2 -2518 A>G polymorphism with breast cancer occurrence and clinical characteristics in a sample of the Polish cohort.

CXCL12-3' G801A polymorphism is not a risk factor for breast cancer.

The CXCL12-3' G801A transition (rs1801157) has been associated with the incidence of breast cancer. However, the contribution of CXCL12-3' G801A polymorphisms in breast cancer development and progression has been controversial. Therefore, we examined the incidence of CXCL12-3' G801A polymorphic variants in patients with breast cancer (n = 193) and controls (n = 199) in a Polish cohort. We observed a trend of slightly increased presence of CXCL12-3' AA and GA genotypes and CXCL12-3'A allele frequency in patients with breast cancer compared with healthy individuals. However, these differences between cases and controls were not statistically significant. Odds ratio (OR) for patients with breast cancer and the CXCL12-3' A/A genotype was 1.898 (95% confidence interval [CI] = 0.6242-5.770, p = 0.2866) and OR of the CXCL12-3' A/A and A/G genotypes was 1.229 (95% CI = 0.8082-1.868, p = 0.3395). OR for the CXCL12-3'A allele frequency was 1.249 (95% CI = 0.8716-1.789, p = 0.2352). Our investigation did not support the CXCL12-3'A gene variant as a risk factor for breast cancer incidence in a sample of the Polish population.

The determination of VEGF and MVD, among patients with primary breast cancer.

The purpose of the study was to ascertain the value of assessment of vascular endothelial growth factor (VEGF) levels and microvessel density, and to search for correlations between them, in women with breast cancer. The assessment considered factors such as the stage of clinical disease advancement--according to International Union Against Cancer, the grade of histological malignancy, status of axillary lymph nodes and the size of the primary tumour. The concentration of VEGF was assessed in the plasma of 103 women with breast cancer, using an immunoenzymatic method (Quantikine test of R&D Systems). Assessment of microvessel density was performed using histopathological immunoperoxidase methods, using an anti-von Willebrand factor antibody (DAKO A/S). A statistically significant relationship was found between rising VEGF levels and microvessel density in women with breast cancer, when compared to values from a control group. A correlation was found between VEGF concentration and microvessel density (MVD) values. Statistically significant differences were found between VEGF levels of patients in stages I, II and III of clinical disease advancement. For MVD, differences were found only between stages I and III. A statistical relationship was also found between VEGF and MVD and tumour size. Similar results were found between VEGF concentrations in women with metastases to the axillary lymph nodes and cytokine levels in women with no metastases. The results of the study suggest that the degree of tumour vascularization and the concentration of VEGF may represent valuable indicators for the assessment of the angiogenic process in women with breast cancer.

[Anticardiolipin and anti-beta2 glycoprotein-1 antibodies patients with breast carcinoma: a pilot study]. / Przeciwciala przeciwkardiolipinowe i przeciwko beta2 glikoproteinie-I u chorych na raka piersi: doniesienie wstepne.

INTRODUCTION: Thrombosis - the main manifestation of antiphospholipid syndrome (APS) - is at the same time observed in some patients with malignancies. OBJECTIVES: Evaluation of prevalence of some antiphospholipid antibodies (aPL) in serum of patients with breast carcinoma and the possible correlation between aPL seropositivity and clinical symptoms. PATIENTS AND METHODS: 40 patients with breast carcinoma and 38 patients with non-malignant diseases of breast were studied. Anticardiolipin antibodies (aCL) and antibodies to beta2 glycoprotein-I (anti-beta2GPI) were detected by ELISA. RESULTS: The aCL as well as anti-beta2GPI were positive in 1 patient with breast carcinoma, who at the same time presented with symptoms of APS. In the control group 2 patients were positive for anti-beta2GPI. CONCLUSIONS: We have not observed a difference of aPL prevalence between the group of patients with breast carcinoma and controls. The association of breast cancer and aPL seropositivity deserves further investigations.

Diagnostic value of measuring serum CA 15-3, TPA, and TPS in women with breast cancer.

INVESTIGATION: The concentrations of CA 15-3, TPA, and TPS were determined in the serum of 90 women with breast cancer MATERIAL/METHODS: Serum CA 15-3 levels were determined by Abbott immunofluorescent tests, TPA concentration using the Byk-Roland immunoluminometric method, and TPS by the BEKI Diagnostics immunoenzymatic method. RESULTS: In the diagnosis of breast cancer, the TPA test had the greatest diagnostic sensitivity. A strong correlation was found between the percentages of women with positive levels of all three markers and advanced stages of breast cancer. A longitudinal evaluation of 42 women who underwent neoadjuvant chemotherapy showed clinical regression of the tumor and a statistically significant reduction in the concentrations of these markers CONCLUSIONS: These results indicate that determining the serum levels of CA 15-3, TPA, and TPS may be used to establish the stage of disease and it provides useful guidance both in deciding whether to treat surgically and in estimating the efficacy of neoadjuvant chemotherapy in patients with breast cancer.

Contribution of protein kinase A and protein kinase C signalling pathways to the regulation of HSD11B2 expression and proliferation of MCF-7 cells.

Contribution of the protein kinase A (PKA) and protein kinase C (PKC) signalling pathways to the regulation of 11beta-hydroxysteroid dehydrogenase type II (HSD11B2) gene expression was investigated in human breast cancer cell line MCF-7. Treatment of the cells with an adenylyl cyclase activator, forskolin, known to stimulate the PKA pathway, resulted in an increase in HSD11B2 mRNA content. Semi-quantitative RT-PCR revealed attenuation of the effect of forskolin by phorbol ester, tetradecanoyl phorbol acetate (TPA), an activator of the PKC pathway. It was also demonstrated that specific inhibitors significantly reduced the effect of activators of the two pathways. Stimulation of the PKA pathway did not affect, whereas stimulation of the PKC pathway significantly reduced MCF-7 cell proliferation in a time-dependent manner. A cell growth inhibitor, dexamethasone, at high concentrations, caused a 40% decrease in proliferation of MCF-7 cells and this effect was abolished under conditions of increased HSD11B2 expression. It was concluded that in MCF-7 cells, stimulation of the PKA signal transduction pathway results in the induction of HSD11B2 expression and that this effect is markedly reduced by activation of the PKC pathway. Activation of the PKC pathway also resulted in inhibition of cell proliferation, while activation of the PKA pathway abolished the antiproliferative effect of dexamethasone. These effects might be due to oxidation of dexamethasone by the PKA-inducible HSD11B2.