Tatoud R, Degeorges A, Prévost G, Hoepffner J L, Gauvillé C, Millot G, Thomas F, Calvo F
Pharmacologie Expérimentale et Clinique, IGM, Paris, France.
Mol Cell Endocrinol. 1995 Sep 22;113(2):195-204. doi: 10.1016/0303-7207(95)03630-p.
We investigated somatostatin receptors (SSTRs) in surgical specimens of prostate cancer and benign prostate hyperplasia (BPH), a normal immortalized epithelial cell line (PNT1), epithelial cancer cell lines, and stromal cells in short-term culture derived from normal and BPH biopsies. Cross-linking studies with 125I-Tyr11-SRIF-14 (125I-SRIF) and the SRIF analog 125I-BIM-23104 identified one major 57-kDa band both in surgical specimens and in epithelial and stromal cells cultures. In membrane-enriched fractions and whole stromal cells from a normal prostate and from one BPH, a single type of SSTR was characterized (Kd = 6.10(-9) and 10(-8) M, respectively, Bmax = 1.6 pmol per mg of proteins). mRNA for SSTR1 was detected in all epithelial and stromal cells tested except for PNT1, while SSTR2 mRNA was detected in one BPH stromal cell culture. BIM-23104 had no effect on the in vitro growth of the epithelial cells tested. Conversely, 10(-10) M BIM-23104 induced >50% growth inhibition of stromal cells after 6 days in culture. These results may have implications for therapeutic strategies using SRIF analogs in BPH and prostate cancer.
我们研究了前列腺癌和良性前列腺增生(BPH)手术标本、正常永生化上皮细胞系(PNT1)、上皮癌细胞系以及源自正常和BPH活检组织的短期培养基质细胞中的生长抑素受体(SSTRs)。用¹²⁵I-Tyr¹¹-SRIF-14(¹²⁵I-SRIF)和生长抑素类似物¹²⁵I-BIM-23104进行的交联研究在手术标本以及上皮和基质细胞培养物中均鉴定出一条主要的57-kDa条带。在来自正常前列腺和一个BPH的富含膜的组分和整个基质细胞中,鉴定出一种单一类型的SSTR(Kd分别为6×10⁻⁹和10⁻⁸M,Bmax为每毫克蛋白质1.6 pmol)。除PNT1外,在所有测试的上皮和基质细胞中均检测到SSTR1的mRNA,而在一种BPH基质细胞培养物中检测到SSTR2的mRNA。BIM-23104对所测试的上皮细胞的体外生长没有影响。相反,在培养6天后,10⁻¹⁰M BIM-23104诱导基质细胞生长抑制>50%。这些结果可能对在BPH和前列腺癌中使用生长抑素类似物的治疗策略具有启示意义。