Devi Gayathri R, Sprenger Cynthia C, Plymate Stephen R, Rosenfeld Ron G
Department of Pediatrics, School of Medicine, Oregon Health Sciences University, Portland, Oregon, USA.
Prostate. 2002 May 1;51(2):141-52. doi: 10.1002/pros.10068.
Insulin-like growth factor binding protein (IGFBP-3) levels are significantly reduced in malignant prostate epithelial cells. In this study, we evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and tumorigenesis.
IGFBP-3 was re-expressed by stable transfection of human IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in which IGFBP-3 levels are undetectable in comparison to the parent epithelial cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics, morphology, propensity to apoptosis, and in vivo tumor formation were studied.
M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density that was threefold lower than control cells and this was associated with marked alteration in cell morphology. Control cells when grown in conditioned media secreted by M12-BP-3 also showed altered morphology compared to when cultured in IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1 peak, decreased levels of neuron specific enolase, and decreased tumor formation in athymic, nude mice.
These data suggest that IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate 51: 141-152, 2002.
胰岛素样生长因子结合蛋白（IGFBP - 3）水平在恶性前列腺上皮细胞中显著降低。在本研究中，我们评估了内源性IGFBP - 3在前列腺癌细胞生长和肿瘤发生中的作用。
通过在人前列腺癌模型M12（一种恶性亚系，与亲代上皮细胞P69相比，IGFBP - 3水平无法检测到）中稳定转染人IGFBP - 3 cDNA来重新表达IGFBP - 3。研究了IGFBP - 3重新表达（M12 - BP - 3）对生长动力学、形态、凋亡倾向和体内肿瘤形成的影响。
M12 - BP - 3细胞分泌IGFBP - 3并在细胞密度比对照细胞低三倍时生长停滞，这与细胞形态的明显改变有关。与在IGFBP - 3免疫耗尽的条件培养基中培养相比，对照细胞在M12 - BP - 3分泌的条件培养基中生长时也显示出形态改变。M12 - BP - 3克隆显示线粒体膜电位改变、PARP裂解增加、亚G1峰增加、神经元特异性烯醇化酶水平降低以及在无胸腺裸鼠中肿瘤形成减少。
这些数据表明IGFBP - 3诱导早期凋亡并在前列腺癌中具有潜在的肿瘤抑制作用。《前列腺》51: 141 - 152, 2002年。
