Role of Androgen Receptor in the Pathogenesis of Prostatic Cancer
Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Fukui Medical School|
OKADA Kenichiro Faculty of Medicine Professor, 医学部, 教授 (60026838)
MIWA Yoshiji Fukui Medical School Faculty of Medicine Research Associate, 医学部, 助手 (10209968)
GOBARA Masaru Fukui Medical School Faculty of Medicine Research Associate, 医学部, 助手 (20186878)
AKINO Hironobu Fukui Medical School Faculty of Medicine Research Associate, 医学部, 助手 (90159335)
|Project Period (FY)
1990 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1990 : ¥1,300,000 (Direct Cost : ¥1,300,000)
|Keywords||Prostatic cancer / DNA ploidy / lectin / Peanut agglutinin / Ulex europaeus-1 / Tumor volume / アンドロゲンレセプター / レクチン染色 / アンドロゲンレセプタ- / 前立腺肥大症|
The major purpose of this project had been the cloning of cDNA of androgen receptor at the start. Before cloning its cDNA by us. Chang. C and collaborators had succeeded in cloning and determined the sequence of cDNA of androgen receptor. So. we changed the strategy of out research and investigated the sugar chains in prostatic cancer by lectin histochemistry. especially peanut agglutinin(PNA). Cellular sugar chains play important roles in a number of cell functions, including cell-cell and cell-matrix interactions, cell surface receptors and cellular regulation. In addition to lectin histochemistry, DNA ploidy patterns and tumor volumes were analezed.
Lectin histochemistry(PNA and Ulex-europaeus 1 : UEA-1) was examined in 33 patients with in cidental prostatic cancer, 41 with stage C and D, 10 with hormone refractory cancer and 24 with benign prostatic hyperplasia(BPH). PNA was reported that the expression of its binding sugar chain was suggested to be modulated by androgen levels. UEA
-1 binding sugar chain was reported to be increased in adenocarcinomas of colon and rectum.
The results were obtained as follows. 1)In BPH, the major binding sites of PNA were basal cells(75% of BPH-cases). UEA-1 staining were none to weak in columnar secretory cells.
2)PNA binding was increased in incidental cancers(stage A1 and A2) cancers in comparison to BPH.In clinically advanced cancers(stage C and D), the intensity of PNA staining was weaker than in incidentalomas.
3)UEA-1 binding was increased significantly in both incidental and advanced cancers more than in BPH.
4)No relations were demonstrated between lectin bindings and cytological grade.
5)The intensity of PNA and UEA-1 staining were strong in 80% and 100% of hormone refractory prostatic cancers, respectively.
6)DNA ploidy patterns had no relations with the intensity of lectin histochemistry. In well-deferentiated incidentalomas, PNA binding sites in cancer cells were different according to DNA ploidy patterns. diploid cancer cells had PNA binding site in apical area, whereas non-diploid one had both in apical and supranuclear areas.
7)The positive corelation was found between the intensity of UEA-1 staning and tumor volume in incidentalomas.
Expression of PNA binding site, Which was reported to be modulated by androgen levels, was increased in incidentalomas more than BPH and clinically advanced cancers. This indicated that androgen and its cellular messengers including androgen receptor might play important roles in carcinogenesis of proatatic cancers. The different PNA binding site in well-differentiated cancer cells were observed according to DNA ploidy patterns. Although DNA ploidy patterns had no relations with the intensity of PNA staining, the qualitative and/or quantative alterations in of the enzymes involved in glycosylation were suggested to have relations to the abnormality in DNA ploidy.
The increased UEA-1 binding sites in cancers and the positive corelation between the intensity of UEA-1 staning and tumor volume in incidentalomas indicated that the expression of UEA-1 binding sugar chains had close relation with tumor growth. Less
Research Output (5results)