Koga M, Kasayama S, Matsumoto K, Sato B
Department of Medicine III, Osaka University Medical School, Japan.
J Steroid Biochem Mol Biol. 1995 Jul;54(1-2):1-6. doi: 10.1016/0960-0760(95)00117-i.
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.
盐野义癌115（SC 115）已被广泛用于分析雄激素依赖性癌症生长的机制。该肿瘤在体内表现出明显的雄激素依赖性生长，并且从SC 115肿瘤中分离出一种在无血清培养条件下其生长受到雄激素显著刺激的细胞系。这种雄激素依赖性生长是通过诱导一种称为雄激素诱导生长因子（AIGF）的肝素结合生长因子介导的。此外，成纤维细胞生长因子受体1（FGFR 1）被鉴定为AIGF的受体。在SC 115细胞中，FGFR 1 mRNA的表达受雄激素上调，这表明这种雄激素诱导的自分泌环在两个位点被雄激素增强。还从这种雄激素依赖性SC 115肿瘤中建立了一种雄激素非依赖性细胞系。这些雄激素非依赖性细胞的生长受到AIGF的刺激，这表明AIGF不仅作为雄激素依赖性细胞的自分泌生长因子起作用，而且作为雄激素非依赖性细胞的旁分泌生长因子起作用。此外，将AIGF表达载体转染到雄激素依赖性细胞中会促进从雄激素依赖性表型向非依赖性表型的转变。因此，AIGF可能在肿瘤进展中起作用。这些结果表明，阻断AIGF活性是一个重要的治疗靶点。实际上，发现一些化合物如肝素和苏拉明可抑制这种雄激素诱导的自分泌环。将结合其可能的临床应用对这些基础观察结果进行讨论。
