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首页> 外文期刊>Molecular urology >Neither fibroblast growth factor-1 nor fibroblast growth factor-2 is an androgen receptor coactivator in androgen-resistant prostate cancer
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Neither fibroblast growth factor-1 nor fibroblast growth factor-2 is an androgen receptor coactivator in androgen-resistant prostate cancer

机译：成纤维细胞生长因子1和成纤维细胞生长因子2都不是雄激素抵抗性前列腺癌中的雄激素受体共激活因子

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We used rat prostate cancer cell stable transfectants that lacked either endogenous fibroblast growth factor (FGF)-1 secondary to constitutive expression of FGF-1 antisense RNA (aFa2-transfectants) or endogenous FGF-2 isoforms secondary to constitutive expression of FGF-2 antisense RNA (bFa9-transfectants) to examine the potential synergistic effects of mitogen and androgen as modulators of proliferation. During culture on 5% charcoal-stripped fetal bovine serum (CS-FBS), FGF-1 caused a 2- to 2.5-fold increase in the proliferation of aFa2-transfectants that lacked endogenous FGF-1 and retained full expression of FGF-2 isoforms. In marked constrast, bFa9-transfectants that lacked FGF-2 isoforms and retained full expression of FGF-1 died with exponential kinetics when cultured on either 5% CS-FBS or 5% FBS in the absence of FGF-2. However, FGF-2 promoted bFa9-transfectant survival and exponential proliferation during culture on either 5% CS-FBS or 5% FBS. The nonmetabolizable androgen R1881 did not affect proliferation of either the aFa2-transfectants, the bFa9-transfectants, or the parental prostate cancer cells used to generate these transfectants. Additionally, neither of the androgen receptor antagonists RU23908 or bicalutamide affected either FGF-1-mediated aFa2-transfectant proliferation or FGF-2-mediated bFa9-transfectant proliferation during culture on 5% CS-FBS. Notably, transient transfection analyses established R1881 concentration-dependent induction of chloramphenicol acetyltransferase activity in both aFa2-transfectants and bFa9-transfectants. Thus, the failure of either androgen or antiandrogen to affect either FGF-mediated or FGF-independent antisense-transfectant proliferation is not attributable to absence of functional androgen receptors. The results indicate that FGF effects in these androgen-resistant antisense transfectants do not involve either androgen-dependent or androgen-independent, mitogen-mediated androgen receptor activation. Our studies show that these rat prostate cancercells are characterized by both retention of functional androgen receptors during development of androgen resistance and mitogen-mediated, autocrine or paracrine (or both) modulated proliferation. These are two prominent properties characteristic of advanced human prostate cancer.
机译：我们使用了大鼠前列腺癌细胞稳定的转染子，该转染子缺乏继发于FGF-1反义RNA组成型表达的内源性成纤维细胞生长因子（FGF）-1或继发于FGF-2反义性组成型表达的内源性FGF-2同工型RNA（bFa9转染子）来检查有丝分裂原和雄激素作为增殖调节剂的潜在协同作用。在5％的木炭剥离的胎牛血清（CS-FBS）上培养期间，FGF-1导致缺乏内源性FGF-1并保留FGF-2完整表达的aFa2转染子的增殖增加2到2.5倍亚型。在明显的对比中，当在无FGF-2的情况下在5％CS-FBS或5％FBS上培养时，缺乏FGF-2同工型并保留FGF-1完整表达的bFa9转染子以指数动力学死亡。但是，FGF-2可以在5％CS-FBS或5％FBS上培养期间促进bFa9转染子的存活和指数增殖。不可代谢的雄激素R1881既不影响aFa2转染子，bFa9转染子或用于生成这些转染子的亲代前列腺癌细胞的增殖。另外，在5％CS-FBS上培养期间，雄激素受体拮抗剂RU23908或比卡鲁胺均不影响FGF-1介导的aFa2转染子增殖或FGF-2介导的bFa9转染子增殖。值得注意的是，瞬时转染分析在aFa2转染子和bFa9转染子中均建立了R1881浓度依赖性的氯霉素乙酰转移酶活性诱导。因此，雄激素或抗雄激素不能影响FGF-介导的或不依赖于FGF的反义-转染子增殖均不归因于缺乏功能性雄激素受体。结果表明，在这些雄激素抗性反义转染子中，FGF的作用不涉及雄激素依赖性或雄激素非依赖性的，有丝分裂原介导的雄激素受体活化。我们的研究表明，这些大鼠前列腺癌细胞的特征在于，在雄激素抵抗的发展过程中保留功能性雄激素受体，以及有丝分裂原介导的自分泌或旁分泌（或两者）调节的增殖。这些是晚期人类前列腺癌的两个突出特性。

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