Basic study on oncogenic mechanism and invasiveness of pituitary tumor

Research Project

Project/Area Number	07671497
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Cerebral neurosurgery
Research Institution	University of Tsukuba
Principal Investigator	TOMONO Yuji Institute of Clinical Medicine, University of Tsukuba, Assitant Professor, 臨床医学系, 助教授 (70110335)
Co-Investigator(Kenkyū-buntansha)	TSUBOI Koji Institute of Clinical Medicine, University of Tsukuba, Lecturer, 臨床医学系, 講師 (90188615)
Project Period (FY)	1995 – 1997
Project Status	Completed (Fiscal Year 1997)
Budget Amount *help	¥2,300,000 (Direct Cost: ¥2,300,000) Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000) Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Keywords	Pituitary tumor / Estrogen receptor / Oncogenic mechanism / Invasiveness / PCR / エストロゲン / 腫瘍化過程 / 過形成 / 遺伝子 / 下垂体腺腫 / ラット
Research Abstract	Pituitary adenomas are benign tumor, and recently its treatment has showed remarkable progress. However, the results in invasive or some functioning adenomas are insufficient, and recurrences are not infrequent yet. To investigate and know its oncogenesis will be useful to develop a new treatment. It is also necessary to find the factors deciding the invasiveness. For the investigation of these points at issue, we investigated changes of estrogen receptors (ER) and DNA by PCR-different display method in the pitutary cells, using estrogen-induced rat pituitary tumor model. The pituitary gland in this model transforms to a tumor through a stage of hyperplasia. The mechanism of this transformation has not been solved yet, and it is considered that this model is suitable to fins out molecular changes. On the problems of the invasiveness, we examined the clinical cases at first, and then investigated the factors related to the cell cycles, i.e., Ki-67 labeling index and p27. The results are as follows : 1. ER of the rat pituitary cells increased at hyperplastic stage followed by decrease at tumor stage by administration of estrogen. This fact suggests that molecular change into tumor occurs in early stage of estrogen administration. 2. A change suggesting mutation was recognized on the DNA of the cells using PCR-DD method. The identification of this change is the subject in future. 3. There is a possibility that Mn-metalloporphyrine (ATN-10) can be used in diagnosis of malignancy of tumors as an agent for MR enhancement. 4. Average Ki-67 labeling index of the invasive adenomas was significantly higher than non-invasive adenomas. It means that adenomas with higher proliferation have higher invasiveness. There was no significance in p27 expression rate between the two groups, and no significant correlation between the two parameters. We need to study further on more direct factors determining invasiveness.