Study on effects of insulin-like growth factor on growth of prostate cancer

胰岛素样生长因子-I（IGF-I）是一种有效的促有丝分裂和诱导分化的多肽生长因子，并且被认为是参与正常和恶性组织的细胞增殖的重要的自分泌-旁分泌因子。最近，IGF-I受体已在人正常前列腺上皮细胞、增生性前列腺细胞和大鼠前列腺癌细胞中得到表征。此外，描述了一个家族的至少六种对IGF具有高结合亲和力的蛋白质，IGF结合蛋白（IGFBP），其不同于IGF受体，并被认为控制IGF的增殖和促有丝分裂作用。雄激素非依赖性细胞系PC-3和TSU-PRI（大津）。乳腺癌细胞系MCF-7细胞系用作IGF响应性的对照细胞系。IGF-I或雄激素对生长的影响 关于我们 通过使用基于四唑盐MTT的酶促还原的测试来评估细胞的生长。条件培养基蛋白在十二烷基硫酸钠-聚丙烯酰胺凝胶上分离并转移到硝酸纤维素纸上，并且通过Western印迹来检测IGFBPs。饱和分析法测定膜透性后IGF-Ⅰ受体含量。IGF-1对MCF-7细胞的刺激呈剂量依赖性（1- 100 ng/ml）。在相同条件下，FGC、LNCaP-r、LNO和PC-3细胞系对IGF-I无反应，而IGF-I轻微刺激大津系的生长。IGF-1中加入雄激素并不影响雄激素依赖性FGC细胞系的细胞生长。高亲和力IGF-I受体在所有测试的细胞系中被证明，FGC系的受体含量低于其他雄激素非依赖性细胞系。所有前列腺癌细胞株均分泌IGFBP-2，而在LNCaP-r、PC-3和大津培养物中也检测到IGFBP-3和/或IGFBP-4，尽管存在高亲和力IGF受体，但除一个例外（大津），IGF-I对所测试的前列腺癌细胞株的细胞增殖没有影响。如对其他组织所述，IGFBP-2可能是抑制这些细胞系中IGF-I生物活性的因子，而一些其他IGFBP，如IGFBP-4可能增强细胞的IGF-I反应性。因此表明IGFBPs调节IGF-I介导的前列腺癌细胞的细胞增殖。少

Insulin-like growth factor-I (IGF-I) is a potent mitogenic and a differentiation inducing polypeptide growth factor, and is considered to be a significant autocrine-paracrine factor involved in cellular proliferation of normal and malignant tissues. Recently, IGF-I receptors have been characterized in human normal prostate epithelial cells, hyperplastic prostate cells, and rat prostate cancer cells. Furthermore, a family of at least six proteins with high binding affinity for IGFs, the IGF binding proteins (IGFBPs), are described which are different form IGF receptors and are considered to control the proliferative and mitogenic effects of IGFs.The androgen-dependent prostatic carcinoma cell line, LNCaP-FGC (FGC), its derived androgen-independent sublines, LNCaP-r and LNO,and the androgen-independent cell lines PC-3and TSU-PRI (TSU) were used. The breast cancer cell line MCF-7 cell line served as control cell line for IGF responsiveness. The effects of IGF-I or androgens on the growth … More of the cells were assessed by the use of a test based on the enzymatic reduction of the tetrazolium salt MTT.Conditioned medium proteins were separated on sodium dodecylsulfate-polyacrylamide gel and transferred to nitrocellulose paper and IGFBPs were detected by Western blotting. IGF-I recceptor content of membrane preparated was determined by saturation analysis. The data were calculated by multiple-point Scatchard analyzes.IGF-I stimulated MCF-7 cells dose-dependently (1-100ng/ml). Under the same conditions FGC,LNCaP-r, LNO,and PC-3 cell lines did not respond to IGF-I,whereas it slightly stimulated growth of the TSU line. Androgen addition to IGF-I did not influence the cell growth of the andfrogen-dependent FGC cell line. High affinity IGF-I receptors were demonstrated in all cell lines lested, the receptor content of the FGC line being lower than the other androgen-independent cell lines. All prostatic cancercell lines secreted IGFBP-2, whereas IGFBP-3 and/or IGFBP-4 were also detected in the medium of LNCaP-r, PC-3 and TSU cultures.In spite of the presence of high affinity IGF receptors, with one exception (TSU), IGF-I had no effect on cell proliferation of the prostatic cancer cell lines tested. As has been described for other tissues, IGFBP-2 may be a factor that inhibits the biological activity of IGF-I in these cell lines, whereas some other IGFBPs, such as IGFBP-4 may enhance IGF-I responsiveness of the cells. It is therefore suggested that IGFBPs regulate IGF-I mediated cell proliferation of prostate cancer cells. Less