Lilja J F, Wu D, Reynolds R K, Lin J
Department of Obstetrics and Gynecology, The University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
Anticancer Res. 2001 May-Jun;21(3B):1969-74.
The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.
AKT蛋白在几种类型的人类癌症中持续激活,这可能在致癌过程中发挥作用。在本研究中,我们检测了一组人子宫内膜癌细胞系和肿瘤样本中AKT的激活情况。两种子宫内膜癌细胞系Ishikawa(ISK)和RL-95以及几个肿瘤样本显示磷酸化AKT水平升高。PTEN在45%的子宫内膜癌中发生突变,是AKT的负调节因子。我们检测了PTEN在ISK和KLE子宫内膜癌细胞中的生长抑制活性。PTEN的表达显著抑制了这两种细胞系的生长。在原代大鼠胚胎成纤维细胞中,PTEN也抑制由ras和c-myc癌基因介导的恶性转化。这两种癌基因在子宫内膜癌中通常发生突变或扩增。这些结果表明,PTEN可能是子宫内膜癌的一种有效治疗药物。