Study on the mechanisms of carcinogenesis of endometrium.

Research Project

Project/Area Number	04670986
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Obstetrics and gynecology
Research Institution	HOKKAIDO UNIVERSITY
Principal Investigator	OKUYAMA Kazuhiko Hokkaido Univ.Hospital, Instructor, 医学部・附属病院, 助手 (40214085)
Co-Investigator(Kenkyū-buntansha)	FUJIMOTO Seiichiro Hokkaido Univ., School of Medicine, Prof., 医学部, 教授 (60001898) 藤野敬史北海道大学, 医学部附属病院, 助手 (20209076) 山田秀人北海道大学, 医学部附属病院, 助手 (40220397)
Project Period (FY)	1992 – 1994
Project Status	Completed (Fiscal Year 1994)
Budget Amount *help	¥2,200,000 (Direct Cost: ¥2,200,000) Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords	bcl-2 / PCNA / endomtrial carcinoma / 子宮内膜癌 / 微小核融合 / 癌抑制遺伝子 / 細胞エイジング / 微少核融合
Research Abstract	In order to investigate the mechanisms of carcinogenesis of endometrium of the uterus, we examined placental tissues which were collected from normal pregnancy and abnormal pregnancy, including intrauterine growth retardation, intrauterine fetal death, abruptio placenta and premature deliveries, and various types of endometrial carcinoma tissues at our department. These tissues were stored at-80 degrees until extraction of DNA and RNA as well as immunohistochemical investigation. PCNA (proliferating cell nuclear antigen) with immunohistochemical methods showed gradual decrease of the expression in placental tissues according to the progress of pregnancy. This phenomenon probably indicated the discontinuation of growth of placenta. On the contrary, bcl-2 showed gradual increase in the amount of cytoplasmic expression according to the progress of pregnancy. At term very strong staining of bcl-2 was detected. Bcl-2 plays an important role in preventing DNA digestion by endonucleases, progr … More amd cell death (apoptosis), resulting in the elongation on cell life presumably through one of the mechanisms of blocking the transport of p53 protein. In endometrial carcinoma cells bcl-2 staining was detected even in nuclear area when the nuclear grade and histological grade increased. This finding strongly suggested that bcl-2 protected endometrial cells from apoptosis resulting in immortalization and carcinogenesis. The next step was to investigate the expression of apoptosis in placental tissues. Apoptosis was detected by electrophoresis in every placental tissue collected at C-section. Interestingly the ladder intensity appeared on the gel differed when compared from the point of view of onset of labor pains. However in endometrial carcinoma tissues it is still unclear whether apoptosis would decrease or not because the amount of apoptosis differed from each tissue. We concluded that bcl-2 might play an important role in control of the span of cell life and also in the carcinogenesis of endometrial cells in conjunction with telomerase activity. Less