子宮内膜におけるテロメレース発現とその異常および発現制御機構の解析(2子宮内膜の機能とその異常)

概要

論文の詳細を見る
Telomerase is a specialized ribonucleotide protein that adds telomeric-repeated sequences to the ends of human chromosome DNA. Activation of telomerase thus prevents progressive shortening of telomeres with cell division and enables cells to overcome replicative senescence associated with severe loss of telomeres. Telomerase is active in the vast majority of tumors, but usually inactivated in normal somatic tissues, probably giving tumor cells a growth advantage over normal cells. Thus, telomerase activation is a critical step for carcinogenesis. In the present study, we found that normal human endometrium express telomerase activity in a menstrual-phase dependent manner, which was localized to epithelial glandular cells. Among subunits comprising telomerase, human telomerase reverse transcriptase (hTERT) was a rate-limiting determinant of the enzymatic activity of telomerase. To understand the molecular mechanisms of telomerase activation in endometrium, we cloned the promoter sequences of hTERT gene and analyzed the transcriptional regulation of hTERT. We found that c-Myc and Sp1 are the majortranscription factors regulating promoter activity of hTERT. We also found that estrogen and progesterone regulate hTERT expression via interaction of ligand-activated receptors with hTERT promoter or activation of mitogen-activated protein (MAP) kinase cascade. Finally, we demonstrated that inhibition of telomerase activity in endometrial cancer cells by introducing antisense human telomerase RNA sequences caused significant growth suppression of the cells. These findings suggest that telomerase activity in human endometrium is critically regulated by c-Myc and Sp1 as well as sex steroid hormones and may play an essntial role in endometrial proliferation in a menstrual cycle.
社団法人日本産科婦人科学会の論文
2000-08-01

子宮内膜におけるテロメレース発現とその異常および発現制御機構の解析(2子宮内膜の機能とその異常)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク