Type-1 insulin-like growth factor receptor reexpression in the malignant phenotype of SV40-T-immortalized human prostate epithelial cells enhances apoptosis.
Type-1 insulin-like growth factor receptor reexpression in the malignant phenotype of SV40-T-immortalized human prostate epithelial cells enhances apoptosis.
复制标题
SV40-T 永生化人前列腺上皮细胞恶性表型中 1 型胰岛素样生长因子受体的重新表达可增强细胞凋亡。
作者：
Plymate,SS;Bae,VL;Maddison,L;Quinn,LS;Ware,JL
作者此前已证明，1型胰岛素样生长因子受体（IGF-1R）在体内人前列腺上皮细胞从良性向恶性转化的过程中减少。此外，在一个详细描述的人类SV40-T永生化人上皮细胞系统中，从永生化但很少致瘤的P69SV40-T细胞系开始，到高度致瘤和转移的M12亚系，IGF-1R数量有类似的减少，从每个细胞2.0×104个受体到每个细胞1.1×103个受体。当使用逆转录病毒表达载体 M12-LISN 在 M12 亚系中将 IGF-1R 重新表达到与 P69SV40-T 亲本细胞系相似的受体数量时，作者证明，与 M12 对照细胞相比，M12-LISN 细胞中软琼脂中的集落形成显着减少（p≤0.01），并且当皮下或前列腺内注射时，体内肿瘤生长和转移减少(p≤0.01)。肿瘤体积的减小并不是由于增殖能力的降低，而是与基线培养物中细胞凋亡的增加以及细胞凋亡诱导剂 6-羟基脲、视黄酸和转化生长因子 β1 的反应有关。
The authors have previously shown that the type 1 insulin-like growth factor receptor (IGF-1R) is decreased in the transformation from benign to malignant human prostate epithelial cells in vivo. Further, in a well-described human SV40-T immortalized human epithelial cell system beginning with the immortalized, but rarely tumorigenic P69SV40-T cell line, to the highly tumorigenic and metastatic M12 subline, there is a similar decrease in IGF-1R number from 2.0×104receptors per cell to 1.1×103receptors per cell. When the IGF-1R was reexpressed in the M12 subline using a retroviral expression vector, M12-LISN, to a receptor number similar to that of the P69SV40-T parental cell line, the authors demonstrated a marked decrease in colony formation in soft agar in the M12-LISN cells vs the M12 control cells (p≤0.01), and a decrease in vivo tumor growth and metastases when injected either subcutaneously or an intraprostatic location (p≤0.01). This decrease in tumor volume was not because of a decrease in proliferative capacity, but was associated with an increase in apoptosis in baseline cultures and in response to the apoptotic-inducing agents 6-hydroxyurea, refinoic acid, and transforming growth factor β1.