Castagnetta L A, Carruba G
Hormone Biochemistry Laboratories, University of Palermo, Italy.
Ciba Found Symp. 1995;191:269-86; discussion 286-9. doi: 10.1002/9780470514757.ch16.
We have studied the response to oestrogen and expression of oestrogen receptors in responsive LNCaP and androgen non-responsive PC3 human prostate cancer cell lines. Growth of LNCaP cells is significantly stimulated by physiological concentrations of oestradiol; this growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone. In contrast, oestradiol significantly inhibits the proliferation of PC3 cells. We also present novel evidence for functional oestrogen binding in LNCaP cells. This evidence was first obtained by means of radioligand binding assays and was further corroborated using: (a) immunocytochemical analysis of oestrogen and progesterone receptors; (b) reverse transcriptase polymerase chain reaction of oestrogen receptor mRNAs; and (c) immunofluorescence of the 27 kDa heat shock protein (Hsp27), which has been reported to be a marker of functional oestrogen receptors. There appeared to be significantly and consistently lower levels of oestrogen receptor expressed in PC3 cells than in LNCaP cells. The observation that oestradiol-induced growth of LNCaP cells is completely reversed by the pure anti-oestrogen ICI 182,780 clearly implies that the biological response of these cells to oestradiol is mediated mainly via its own receptor. On the other hand, use of a neutralizing antibody against transforming growth factor (TGF)-beta 1 results in a remarkable increase in the growth of PC3 cells; this effect is almost completely abolished after the addition of oestradiol. This suggests that the oestradiol-induced growth inhibition may be mediated by TGF-beta 1. These results suggest that the current model for hormone-dependence of human prostatic carcinoma should be revised. This is of special concern, because recent data indicate that prostate cancer has become the most prevalent cancer and the second principal cause of cancer death in western countries.
我们研究了雌激素反应性LNCaP和雄激素非反应性PC3人前列腺癌细胞系对雌激素的反应以及雌激素受体的表达。生理浓度的雌二醇能显著刺激LNCaP细胞的生长；这种生长增加似乎与睾酮或二氢睾酮诱导的生长增加相当。相比之下，雌二醇显著抑制PC3细胞的增殖。我们还提供了LNCaP细胞中功能性雌激素结合的新证据。这一证据首先通过放射性配体结合试验获得，并通过以下方法进一步证实：(a)雌激素和孕激素受体的免疫细胞化学分析；(b)雌激素受体mRNA的逆转录聚合酶链反应；(c)27 kDa热休克蛋白(Hsp27)的免疫荧光，据报道它是功能性雌激素受体的标志物。PC3细胞中雌激素受体的表达水平似乎明显且持续低于LNCaP细胞。纯抗雌激素ICI 182,780能完全逆转雌二醇诱导的LNCaP细胞生长，这一观察结果清楚地表明，这些细胞对雌二醇的生物学反应主要是通过其自身受体介导的。另一方面，使用针对转化生长因子(TGF)-β1的中和抗体可导致PC3细胞生长显著增加；添加雌二醇后，这种效应几乎完全消失。这表明雌二醇诱导的生长抑制可能由TGF-β1介导。这些结果表明，人类前列腺癌激素依赖性的当前模型应予以修订。这一点特别值得关注，因为最近的数据表明，前列腺癌已成为西方国家最常见的癌症和癌症死亡的第二大主要原因。
