Tokunaga E, Maehara Y, Oki E, Kitamura K, Kakeji Y, Ohno S, Sugimachi K
Cancer Center, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
Cancer Lett. 2000 Apr 28;152(1):15-22. doi: 10.1016/s0304-3835(99)00434-6.
p33(ING1) is a novel candidate tumor suppressor and its overexpression induces growth arrest or apoptosis in different cell lines. These functions of p33(ING1) depend largely on the activity of p53, and p53-dependent activation of the transcription from the p21/WAF1 promoter also requires p33(ING1). We examined the expression of ING1 mRNA in breast cancer cell lines and clinical breast cancer tissues, using quantitative RT-PCR and real time TaqMan technology. In breast cancer cell lines, ING1 mRNA was expressed at almost the same level. However, in a comparison between the cancer and matched normal tissues, a significant decrease in ING1 mRNA expression was found in 17 of 24 (70.8%) breast cancer tissues. We also examined the correlation between ING1 mRNA expression and p53 expression. There was a significant decrease of ING1 mRNA in nine of 15 tumors negative for p53 immunostaining, most of which were considered to have wild type p53. In these tumors, p53 may not function in case of a decreased expression of p33(ING1), and the lack of cell cycle regulation may correlate with the carcinogenesis and tumor progression.
p33(ING1)是一种新型的候选肿瘤抑制因子,其过表达可在不同细胞系中诱导生长停滞或凋亡。p33(ING1)的这些功能很大程度上取决于p53的活性,并且p21/WAF1启动子转录的p53依赖性激活也需要p33(ING1)。我们使用定量逆转录聚合酶链反应(RT-PCR)和实时TaqMan技术检测了乳腺癌细胞系和临床乳腺癌组织中ING1 mRNA的表达。在乳腺癌细胞系中,ING1 mRNA的表达水平几乎相同。然而,在癌组织与配对的正常组织的比较中,24例乳腺癌组织中有17例(70.8%)发现ING1 mRNA表达显著降低。我们还检测了ING1 mRNA表达与p53表达之间的相关性。在15例p53免疫染色阴性的肿瘤中有9例ING1 mRNA显著降低,其中大多数被认为具有野生型p53。在这些肿瘤中,p33(ING1)表达降低时p53可能无法发挥作用,并且细胞周期调控的缺乏可能与致癌作用和肿瘤进展相关。