ABSTRACT
The role of chemokines and the growth factors has been extensively analyzed both in cancer risk and tumor progression. The transforming growth factor beta (TGF-ß) and chemokine (C-X-C motif) receptor 4 (CXCR4) genes are implicated in several diseases, including breast cancer. Genomic DNA was obtained from 21 samples of peripheral blood or from normal tissue, previously fixed in formalin and embedded in paraffin for TGF-ß T869C polymorphism analyses. Total cellular RNA was extracted from the same 21 patients, but from fresh tissue (tumor and adjacent healthy from the same breast) for expression analysis by Real Time PCR. No significant differences were observed in genotype distribution according to clinicopathological characteristics. Transforming growth factor beta (TGF-ß) mRNA expression was assessed according to T869C polymorphism and CC patients presented a higher TGF-ß expression but not significant when compared to other genotypes (p = 0.064). A positive correlation was observed in relative mRNA expressions of CXCR4 and TGF-ß (p = 0.020). It is known that overexpression of TGF-ß by both tumor and stromal tissue can facilitate the development of metastases, mainly by TGF-ß stimulated angiogenesis and increased tumor cell motility. Our findings suggested a role of these genes as progression markers for breast carcinoma.
Subject(s)
Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Gene Expression , Polymorphism, Single Nucleotide , Receptors, CXCR4/metabolism , Transforming Growth Factor beta1/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Female , Genetic Association Studies , Humans , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, CXCR4/genetics , Sequence Analysis, DNAABSTRACT
The serotonergic system may be involved in smoking behavior since the intake of nicotine increases serotonin secretion in the CNS. Moreover, evidence supporting the beneficial effect of selective serotonin reuptake for quitting smoking suggesting that the serotonin transporter (5-HTT) is a plausible target for the understanding and elucidation of smoking behavior. The transcriptional activity of its human gene (SLC6A4) is modulated by a polymorphism described in the second intron, the STin2 VNTR, which thus may interfere with 5-HTT synthesis. In this study was analyzed the polymorphism STin2 VNTR of 60 smokers male patients diagnosed for oral carcinoma, 61 male smokers without cancer and 65 non-smoker healthy blood donors. The STin2. 9 allele carriers were more present in smoker groups (with cancer and without cancer, respectively) than in the non-smoker (OR = 7.11, 95% CI = 0.83-60.91 and OR = 24.73; IC 95% = 3.17-192.66). Conversely, individuals carrying allele 10 were more prevalent in non-smokers compared with smokers (oral cancer patients and individuals without cancer, respectively), showing a protective factor of this allele (OR = 0.56; 95% CI = 0.24-1.33 and OR = 0.46; 95% CI = 0.20-1.07). This is the first report of a study assessing the importance of STin2 VNTR smoking behavior in Brazilian individuals and the association of STin2. 9 allele carriers in nicotine dependence. It is suggested that individuals with low serotonin concentration in the central nervous system, probably due to the presence of the allele for high expression of 5-HTT,especially STin2. 9, were more susceptible to nicotine dependence. Moreover, individuals with the 10 allele might have less risk for nicotine dependence.