Project/Area Number |
63480361
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Urology
|
Research Institution | KAGAWA MEDICAL SCHOOL |
Principal Investigator |
WADA Fumio Kagawa Medical School, Department of Endocrinology, Professor, 医学部, 教授 (20028385)
|
Co-Investigator(Kenkyū-buntansha) |
MATUO Yuhsi Kagawa Medical School, Department of Endocrinology, Research Associate, 医学部, 助手 (30093462)
NISHI Nozomu Kagawa Medical School, Department of Endocrinology, Research Associate, 医学部, 助手 (10145047)
|
Project Period (FY) |
1988 – 1989
|
Project Status |
Completed (Fiscal Year 1989)
|
Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥4,100,000 (Direct Cost: ¥4,100,000)
|
Keywords | Prostate / Growth factor / Serum-free primary culture / BPH / Cancer / Metastasis / Osteoblast / 前立腺癌 / 細胞株 / TGF-β / 培養細胞 / 初代培養 / IGFーII / CHAPS / HBGF |
Research Abstract |
The present study was designed to reveal the role of growth factors in proliferation of normal and transformed prostate cells and osteoblastic bony metastasis of prostate cancer. The study included 1) analysis and purification of growth factors in human and rat prostates, 2) determination of growth requirements of rat prostate cells in vitro using serum-free primary culture, 3) identification and examination of pysiological role of growth factors produced by a metastatic cell line derived from rat prostate adenocarcinoma. Heparin-binding growth factor (HBGF) was identified as a major growth factor in human prostates. The contents of HBGF were high in tumor tissues, especially in benign prostatic hypertrophy (BPH). The growth factor was characterized as HBGF-2 (basic fibroblast growth factor) using partially purified preparation. In addition to IIBGF-2, human prostate cancer contained a growth factor capable of stimulating DNA synthesis in osteoblasts (osteoblast growth factor). High mol
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ecular weight epidermal growth factor (HMW-EGF) and EGF were purified from adult rat dorsolateral prostate as major growth factors. Amino acid sequence analysis of the purified samples revealed that post-translational processing of EGF precursor protein in the prostate was different from that in the submaxillary gland. There was a relationship between the contents of the growth factors (HMW-EGF plus EGF) and proliferation of prostate epithelial cells in vivo. Serum-free primary culture techniques for rat prsotate epithelial and stromal cells have been established. Growth of the epithelial cells was stimulated by EGF, insulin, cholera toxin and soy bean trypsin inhibitor but not androgen under the conditions used. The growth requirements of the stromal cells were quite different from those of the epithelial cells. Insuilin-like growth factor II (IGF-II) and transforming growth factor beta (TGF-beta) were found in the conditioned medium of a metastatic cell line (AT-3) established from rat prostate cancer (Dunning tumor). ICF-II and TGF-beta were supposed to participate in growth of AT-3 itself and osteoblastic bony metastasis, respectively. These results suggested that growth factors in the prostates play significant roles in normal and pathologic growth of prostate cells and in osteoblastic bony metastasis of prostate cancer. Less
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