PC-cell derived growth factor (PCDGF) is an 88-kDa growth factor originally purified from the highly tumorigenic teratoma PC cell line and corresponds to the epithelin/granulin precursor. In teratoma cells, PCDGF expression was shown to be essential for tumorigenicity. We have reported that PCDGF was expressed in estrogen receptor-positive (ER(+)) human mammary epithelial cells in an estrogen-dependent fashion. In this study, we have investigated PCDGF expression in human mammary epithelial cell lines ranging from immortalized nontumorigenic cells to ER(+) and ER(-) breast carcinoma cells. Northern and Western blot analyses indicated that PCDGF mRNA and protein expression was low in nontumorigenic cells and increased in human breast carcinomas cell lines in a positive correlation with their tumorigenicity. Treatment of the ER(-) MDA-MB-468 cells with anti-PCDGF neutralizing antibody resulted in a dose-dependent inhibition of their proliferation, suggesting that secreted PCDGF acted as an autocrine growth factor for breast carcinoma cells. We then examined the in vitro and in vivo growth properties of MDA-MB-468 cells, where PCDGF expression had been inhibited by antisense PCDGF cDNA transfection. Inhibition of PCDGF expression resulted in a reduced proliferation rate in vitro and a 60-80% reduction in colony formation. Tumor formation in vivo was dramatically inhibited in antisense cells with a 90% inhibition of tumor incidence and tumor weight. These results demonstrate the importance of PCDGF overexpression for the proliferation and tumorigenicity of ER(-) breast carcinomas and suggest that PCDGF overexpression may play an important role in human breast cancer.

译文

PC细胞衍生的生长因子 (PCDGF) 是一种88 kDa的生长因子,最初是从高度致瘤性畸胎瘤PC细胞系中纯化的,对应于上皮蛋白/颗粒蛋白前体。在畸胎瘤细胞中,PCDGF表达被证明对致瘤性至关重要。我们已经报道了PCDGF以雌激素依赖的方式在雌激素受体阳性 (ER ()) 的人乳腺上皮细胞中表达。在这项研究中,我们研究了从永生化的非致瘤细胞到ER () 和ER(-) 乳腺癌细胞的人乳腺上皮细胞系中PCDGF的表达。Northern和Western印迹分析表明,PCDGF mRNA和蛋白表达在非致瘤细胞中较低,而在人乳腺癌细胞系中增加,与其致瘤性呈正相关。用抗PCDGF中和抗体处理ER(-) MDA-MB-468细胞导致其增殖的剂量依赖性抑制,表明分泌的PCDGF充当乳腺癌细胞的自分泌生长因子。然后,我们检查了MDA-MB-468细胞的体外和体内生长特性,其中PCDGF表达已被反义PCDGF cDNA转染抑制。PCDGF表达的抑制导致体外增殖速率降低和菌落形成减少60-80%。在反义细胞中,体内的肿瘤形成被显著抑制,90% 抑制肿瘤发生率和肿瘤重量。这些结果证明了PCDGF过表达对ER(-) 乳腺癌的增殖和成瘤性的重要性,并表明PCDGF过表达可能在人类乳腺癌中起重要作用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录