Sprenger C C, Damon S E, Hwa V, Rosenfeld R G, Plymate S R
Geriatric Research Education and Clinical Center, VAPSHCS, Seattle/Tacoma, Washington 98493, USA.
Cancer Res. 1999 May 15;59(10):2370-5.
Insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) has been shown to have decreased expression in the progression from benign to malignant prostate epithelial cells (V. Hwa et al., J. Clin Endocrinol. Metab., 83: 4355-4362, 1998). The present study was undertaken to determine the effects of the re-expression of IGFBP-rP1 in a cell line from a model of human prostate cancer, M12, in which IGFBP-rP1 expression had been demonstrated to decrease from the parent epithelial cell, P69, to the malignant subline, M12. An IGFBP-rP1 cDNA encoding the protein was transfected into M12 cells in a plasmid that resulted in constitutive-expression of IGFBP-rP1. Clones of transfected M12 cells were selected for low (L) and high (H) levels of expression, and the plasmid vector alone was transfected into M12 as a control. After transfection, there was a marked alteration in the morphology of the M12 cells such that the H clones had an elongated appearance when compared with the M12 control cells. The M12 clones overexpressing IGFBP-rP1 had a dose-related increase in population doubling time, decreased colony formation in soft agar, an increased propensity to undergo apoptosis in response to 6-hydroxyurea, and decreased tumor formation in male athymic, nude mice. These data suggest that IGFBP-rP1 may have a suppressive effect on prostate cancer development.
胰岛素样生长因子结合蛋白相关蛋白-1（IGFBP-rP1）已被证明在前列腺上皮细胞从良性向恶性进展过程中表达降低（V. Hwa等人，《临床内分泌与代谢杂志》，83: 4355 - 4362，1998）。本研究旨在确定在人前列腺癌模型的细胞系M12中重新表达IGFBP-rP1的效果，在该模型中，已证明IGFBP-rP1的表达从亲本上皮细胞P69到恶性亚系M12有所降低。将编码该蛋白的IGFBP-rP1 cDNA转染到M12细胞中，所用质粒可导致IGFBP-rP1的组成型表达。选择转染的M12细胞克隆，使其表达水平低（L）和高（H），并将仅质粒载体转染到M12中作为对照。转染后，M12细胞的形态有明显改变，与M12对照细胞相比，H克隆呈现出细长的外观。过表达IGFBP-rP1的M12克隆在群体倍增时间上有剂量相关的增加，在软琼脂中的集落形成减少，对6-羟基脲诱导的凋亡倾向增加，并且在雄性无胸腺裸鼠中的肿瘤形成减少。这些数据表明IGFBP-rP1可能对前列腺癌的发展具有抑制作用。
