Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7
Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7
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DOI：
10.1074/jbc.274.52.37461
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发表时间：
1999-12-24
影响因子：
4.8
通讯作者：
Fujii, T
中科院分区：
文献类型：
--
作者：
Hishikawa, K;Oemar, BS;Fujii, T
结缔组织生长因子(CTGF)是一个新出现的CCN基因家族成员，与多种与纤维增生性疾病相关的疾病有关，包括硬皮病和动脉粥样硬化。CTGF在人类癌症中的功能在很大程度上是未知的。我们现在证明了CTGF可以诱导人乳腺癌细胞株MCF-7的凋亡。MCF-7细胞中CTGF mRNA完全缺失，但在转化生长因子-β(TGF-β)作用下明显诱导表达。转化生长因子-β单独诱导MCF-7细胞凋亡，CTGF反义寡核苷酸可逆转这一作用。瞬时转染的MCF-7细胞中CTGF基因过表达可显著促进细胞凋亡。此外，通过DNA片段、TdT介导的dUTP生物素缺口末端标记、流式细胞仪分析和Hoechst 33258细胞核染色，证明重组CTGF蛋白显著促进了MCF-7细胞的凋亡。重组CTGF对Bar蛋白表达无明显影响，但显著降低Bcl2蛋白表达。综上所述，这些结果表明CTGF是人乳腺癌细胞系MCF-7细胞凋亡的主要诱导者，而转化生长因子-β诱导的MCF-7细胞凋亡部分是由CTGF介导的。
Connective tissue growth factor (CTGF) is a member of an emerging CCN gene family that is implicated in various diseases associated with fibro-proliferative disorder including scleroderma and atherosclerosis. The function of CTGF in human cancer is largely unknown. We now show that CTGF induces apoptosis in the human breast cancer cell line MCF-7. CTGF mRNA was completely absent in MCF-7 but strongly induced by treatment with transforming growth factor beta (TGF-beta). TGF-beta by itself induced apoptosis in MCF-7, and this effect was reversed by co-treatment with CTGF antisense oligonucleotide. Overexpression of CTGF gene in transiently transfected MCF-7 cells significantly augmented apoptosis. Moreover, recombinant CTGF protein significantly enhanced apoptosis in MCF-7 cells as evaluated by DNA fragmentation, Tdt-mediated dUTP biotin nick end-labeling staining, flow cytometry analysis, and nuclear staining using Hoechst 33258. Finally, recombinant CTGF showed no effect on Bar protein expression but significantly reduced Bcl2 protein expression. Taken together, these results suggest that CTGF is a major inducer of apoptosis in the human breast cancer cell line MCF-7 and that TGF-beta-induced apoptosis in MCF-7 cells is mediated, in part, by CTGF.