Effects Of BRCA1 Gene On HTERT Transcription In Human Breast Cancer

Breast cancer is one of the most common malignant tumors in woman. The incidence of breast cancer has been on rise in recent 20 years, which seriously destroy woman health. Previous study showed that telomerase is associated with early onset of breast cancer. As the catalytic subunit of telomerase, hTERT, is very important to display activity of telomerase. Therefore the investigation of hTERT transcription is very helpful to disclose the partial mechanism of carcinogenesis of breast cancer. BRCA1 gene is a novel tumor surpressor gene discovered recently. Previous study show that BRCA1 is not only associated with hereditary breast cancer, but also with part of sporadic breast cancer. Some experts presumed that BRCA1 is correlated with transcription of hTERT when studying the mutation of E-box in promoter of hTERT gene. However it is still unclear whether BRCA1 gene is really important in transcription of hTERT.In order to recognize the effect of BRCA1 gene on transcription of hTERT, we investigate expression of hTERT mRNA and BRCA1 protein in breast cancer and analyze relationship between them, then observe effects of overexpression of BRCA1 on hTERT expression.In our study, we detected expression of hTERT mRNA and BRCA1 protein by RT-PCR and immunohistochemistry in 43 cases of breast cancer tissue and 40 cases of paracancerous tissues. Next, we transfected pCDNA3.1-BRCA1 plasmid into MCF-7 cell line by lipofectin reagent and observed changes of hTERT protein expression by Western blot. Proliferation of MCF-7 was examined by MTT test.The results showed that in total 41 cases of breast cancer, thirty cases were positive in hTERT mRNA expression and positive rate was 75.0%. Only two in 40 cases of paracancerous tissue were found hTERT mRNA expression and positive rate was 5.0%. Significant difference exited in these two groups. In 41 cases of breast cancer tissue, 15 cases were positive in BRCA1 expression (positive rate 34.8%). Thirty-one in 40 cases of paracancerous tissue were positive in expression of BRCA1 (positive rate77.5%). Obviousdifference exited in two groups. There was strong relation between expression of BRCA1 protein and hTERT mRNA. Western blot showed expression of BRCA increased and expression of hTERT protein decreaseed after pCDNA3.1-BRCAl plasmid was transfected into MCF-7 cell line. MTT test also showed that overexpression of BRCA1 may obviously inhibit proliferation sharply in MCF-7 cell after transfection.Taken together, we found that BRCA1 protein was closely associated with hTERT transcription in breast cancer. Overexpression of BRCA1 may inhibit the expression of hTERT in breast cancer and proliferation of MCF-7 cell, which may play an important role in carcinogenesis of breast cancer.