Telomerase expression within the normal and cancerous human mammary gland.

摘要

The enzyme telomerase catalyzes the de novo synthesis of telomere repeats, thereby maintaining telomere length, which is necessary for unlimited cellular proliferation. Telomerase Reverse Transcriptase (TERT), the catalytic domain of telomerase, is the rate-limiting factor for telomerase activity and is expressed in virtually all tumors. Thus, TERT has been proposed as a marker with diagnostic and prognostic potential in breast cancer, as well as a basis for breast cancer therapeutics. In these contexts, it is important to define the sites and extent of TERT expression with the normal and cancerous human breast tissues.; The broad objective of the work contained herein was to develop a better understanding of the effects of telomerase on breast cancer cell immortalization and tumorigenesis. This was achieved through the investigation of the histological and molecular anatomy of breast tumors with respect to telomerase using newly developed molecular techniques, tools and assays; i.e., real-time RT-PCR, in situ hybridization, promoter-reporter adenoviruses and primary cell culture. Using these new assays, telomerase expression within the normal and cancerous human mammary gland was investigated to assess the levels and effects of telomerase expression.