Molecular mechanism of androgen-dependent growth in transformed cells. Pathway from basic science to clinical application.
Shionogi carcinoma 115 (SC 115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. This tumor exhibits marked androgen-dependent growth in vivo and one cell line whose growth is markedly stimulated by androgen in serum-free culture condition is isolated from SC 115 tumor. This androgen-dependent growth is mediated through an induction of heparin binding growth factor termed as androgen-induced growth factor (AIGF). In addition, fibroblast growth factor receptor 1 (FGFR 1) is identified as a receptor for AIGF. The expression of FGFR 1 mRNA is up-regulated by androgen in SC 115 cells, indicating that this androgen-inducible autocrine loop is potentiated at two sites by androgen. An androgen-independent cell line is also established from this androgen-dependent SC 115 tumor. The growth of these androgen-independent cells is stimulated by AIGF, indicating that AIGF acts not only as an autocrine growth factor to androgen-dependent cells but also as a paracrine growth factor to androgen-independent cells. In addition, transfection of AIGF expression vector into androgen-dependent cells results in a facilitation of conversion from androgen-dependent to -independent phenotype. Thus, AIGF might play a role from tumor progression. These results indicate that a blockade of AIGF activity is an important therapeutic target. Actually, some compounds such as heparin and suramin are found to inhibit this androgen-induced autocrine loop. These basic observations will be discussed in relation to their possible clinical application.
Koga
M
M
Department of Medicine III, Osaka University Medical School, Japan.
Kasayama
S
S
Matsumoto
K
K
Sato
B
B
D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016415:Sequence Alignment; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D006133:Growth Substances; D009363:Neoplasm Proteins; D051524:Fibroblast Growth Factor 8; D013498:Suramin; D005346:Fibroblast Growth Factors