1. Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer
- Author
-
Susan A. Burchill, Rawiah A. Alsiary, Nicholas Griffin, Anke Brüning-Richardson, Sandra M. Bell, Jacquelyn Bond, Richard Hutson, Ewan E. Morrison, and Samantha C. Brownhill
- Subjects
0301 basic medicine ,Telomerase ,endocrine system diseases ,Gene Expression ,Cell Cycle Proteins ,Nerve Tissue Proteins ,Kaplan-Meier Estimate ,Carcinoma, Ovarian Epithelial ,Biology ,Isozyme ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Cell Line, Tumor ,Gene expression ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Genes, Tumor Suppressor ,splice ,Telomerase reverse transcriptase ,Neoplasms, Glandular and Epithelial ,neoplasms ,Ovarian Neoplasms ,BRCA1 Protein ,Wild type ,Cancer ,General Medicine ,medicine.disease ,Isoenzymes ,Cytoskeletal Proteins ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,Suppressor ,Female ,Transcriptome - Abstract
Aims The aim of this study was to explore the correlation of hTERT splice variant expression with MCPH1/BRIT1 and BRCA1 expression in epithelial ovarian cancer (EOC) samples. Background Telomerase activation can contribute to the progression of tumors and the development of cancer. However, the regulation of telomerase activity remains unclear. MCPH1 (also known as BRIT1, BRCT-repeat inhibitor of hTERT expression) and BRCA1 are tumor suppressor genes that have been linked to telomerase expression. Methods qPCR was used to investigate telomerase splice variants, MCPH1/BRIT1 and BRCA1 expression in EOC tissue and primary cultures. Results The wild type α+/β+ hTERT variant was the most common splice variant in the EOC samples, followed by α+/β− hTERT, a dominant negative regulator of telomerase activity. EOC samples expressing high total hTERT demonstrated significantly lower MCPH1/BRIT1 expression in both tissue (p = 0.05) and primary cultures (p = 0.03). We identified a negative correlation between MCPH1/BRIT1 and α+/β+ hTERT (p = 0.04), and a strong positive association between MCPH1/BRIT1 and both α−/β+ hTERT and α−/β− hTERT (both p = 0.02). A positive association was observed between BRCA1 and α−/β+ hTERT and α−/β− hTERT expression (p = 0.003 and p = 0.04, respectively). Conclusions These findings support a regulatory effect of MCPH1/BRIT1 and BRCA1 on telomerase activity, particularly the negative association between MCPH1/BRIT1 and the functional form of hTERT (α+/β+).
- Published
- 2018
- Full Text
- View/download PDF