Tanaka A, Miyamoto K, Minamino N, Takeda M, Sato B, Matsuo H, Matsumoto K
Department of Pathology, Osaka University Medical School, Japan.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8928-32. doi: 10.1073/pnas.89.19.8928.
An androgen-dependent mouse mammary carcinoma cell line (SC-3) requires androgen for growth stimulation. We have shown previously that androgen acts on SC-3 cells to induce secretion of a fibroblast growth factor (FGF)-like growth factor, which in turn stimulates growth of the cells in an autocrine manner. In this study, the androgen-induced growth factor (AIGF) was purified from a conditioned medium of SC-3 cells stimulated with testosterone. cDNA cloning of AIGF by use of its partial amino acid sequence data revealed that AIGF is a distinctive FGF-like growth factor. An AIGF cDNA (pSC17) encodes a 215-amino acid protein with a putative signal peptide, which shares 30-40% homology with known members of the FGF family. The AIGF mRNA was markedly induced by 10 nM testosterone in Northern blot analysis. Expression of AIGF cDNA in mammalian cells clearly showed remarkable stimulatory effects of AIGF on growth of SC-3 cells in the absence of androgen. Thus, it is clear that the androgen-induced growth of SC-3 cells is mediated in an autocrine manner by AIGF, which is secreted by the tumor cells themselves in response to hormonal stimuli.
一种雄激素依赖性小鼠乳腺癌细胞系（SC-3）需要雄激素来刺激生长。我们之前已经表明，雄激素作用于SC-3细胞，诱导分泌一种成纤维细胞生长因子（FGF）样生长因子，该生长因子进而以自分泌方式刺激细胞生长。在本研究中，从用睾酮刺激的SC-3细胞的条件培养基中纯化了雄激素诱导生长因子（AIGF）。利用其部分氨基酸序列数据对AIGF进行cDNA克隆，结果显示AIGF是一种独特的FGF样生长因子。一个AIGF cDNA（pSC17）编码一个具有推定信号肽的215个氨基酸的蛋白质，它与FGF家族的已知成员具有30%-40%的同源性。在Northern印迹分析中，10 nM睾酮显著诱导了AIGF mRNA的表达。在哺乳动物细胞中表达AIGF cDNA清楚地表明，在没有雄激素的情况下，AIGF对SC-3细胞的生长具有显著的刺激作用。因此，很明显，SC-3细胞的雄激素诱导生长是以自分泌方式由AIGF介导的，AIGF是肿瘤细胞自身响应激素刺激而分泌的。
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