Furnari F B, Lin H, Huang H S, Cavenee W K
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093-0660, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84. doi: 10.1073/pnas.94.23.12479.
Deletions of all or part of chromosome 10 are the most common genetic alterations in high-grade gliomas. The PTEN gene (also called MMAC1 and TEP1) maps to chromosome region 10q23 and has been implicated as a target of alteration in gliomas and also in other cancers such as those of the breast, prostate, and kidney. Here we sought to provide a functional test of its candidacy as a growth suppressor in glioma cells. We used a combination of Northern blot analysis, protein truncation assays, and sequence analysis to determine the types and frequency of PTEN mutations in glioma cell lines so that we could define appropriate recipients to assess the growth suppressive function of PTEN by gene transfer. Introduction of wild-type PTEN into glioma cells containing endogenous mutant alleles caused growth suppression, but was without effect in cells containing endogenous wild-type PTEN. The ectopic expression of PTEN alleles, which carried mutations found in primary tumors and have been shown or are expected to inactivate its phosphatase activity, caused little growth suppression. These data strongly suggest that PTEN is a protein phosphatase that exhibits functional and specific growth-suppressing activity.
10号染色体全部或部分缺失是高级别胶质瘤中最常见的基因改变。PTEN基因（也称为MMAC1和TEP1）定位于染色体区域10q23，并且已被认为是胶质瘤以及其他癌症（如乳腺癌、前列腺癌和肾癌）中发生改变的一个靶点。在此，我们试图对其作为胶质瘤细胞生长抑制因子的候选资格进行功能测试。我们结合使用Northern印迹分析、蛋白质截短检测和序列分析来确定胶质瘤细胞系中PTEN突变的类型和频率，以便我们能够确定合适的受体细胞，通过基因转移来评估PTEN的生长抑制功能。将野生型PTEN导入含有内源性突变等位基因的胶质瘤细胞中会导致生长抑制，但对含有内源性野生型PTEN的细胞没有影响。PTEN等位基因的异位表达，这些等位基因携带在原发性肿瘤中发现的突变，并且已显示或预期会使其磷酸酶活性失活，几乎不会引起生长抑制。这些数据强烈表明PTEN是一种具有功能性和特异性生长抑制活性的蛋白磷酸酶。
