ABSTRACT
ABSTRACT NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Down-Regulation , Gene Expression , Homeodomain Proteins/genetics , PTEN Phosphohydrolase/genetics , Prostatic Neoplasms/genetics , Transcription Factors/genetics , Carcinogenesis/genetics , Disease Progression , Electrophoresis, Gel, Two-Dimensional , Genetic Markers , Homeodomain Proteins/analysis , PTEN Phosphohydrolase/analysis , Real-Time Polymerase Chain Reaction , Reference Values , Temperature , Transition Temperature , Transcription Factors/analysisABSTRACT
Aims: Progressive loss of cell cycle control is an important feature on the colorectal cancer. CDKN1A gene encoded p21 protein that’s one of the cyclin-dependent kinase inhibitors, plays a key role in regulating the cell cycle. The aim of this study was toinvestigate associations of the CDKN1A gene polymorphism rs762624 and rs3176336 with risk of colorectal cancer in an Iranian population. Methods: A case-controls study was conducted to investigate the association of polymorphism rs3176336 and rs762624, with colorectal cancer risk in Iranian population. In this study 150 cases of sporadic CRC and 150 healthy controls were recruited, genomic DNA were extracted from peripheral blood, the genotypes were determined using the polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP) method and the result was validated by direct sequencing. Results: The rs762624 frequencies of the AA, AC, and CC genotypes among cases were 9.3%, 74.7%, and 16%, respectively, while in controls genotype frequencies were 10%, 74%, and 16%, respectively. The rs3176336 frequencies of the AA, AC, and CC genotypes among cases were 29.3%, 18% and 52.7%, respectively, while in controls genotype frequencies were18%, 20%, and 62%, respectively. No association was found for the CDKN1A rs3176336 AT/AA genotype (Adjusted odds ratio (OR), 0.726, 95% confidence interval (CI), 0.365–1.443 for AT genotype; OR, 1.67, 95% CI, 0.754–3.702 for AA genotype) with risk of colorectal cancer, compared with the TT genotype. In our research, we could not found significant relation between stage of colorectal cancer and genotypes of rs762624 and rs3176336 polymorphisms (p=0.081, p=0.988). Conclusion: Present data do not confirm association of rs3176336 and rs762624 polymorphisms with susceptibility of Iranian to colorectal cancer.