The expanding role of PTEN in neoplasia: a molecule for all seasons? Commentary re: M. A. Davies, et al., Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin. Cancer Res., 8: 1904-1914, 20
The expanding role of PTEN in neoplasia: a molecule for all seasons? Commentary re: M. A. Davies, et al., Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin. Cancer Res., 8: 1904-1914, 20
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发表时间：
2002-06
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通讯作者：
Magalí Fernández;C. Eng
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作者：
Magalí Fernández;C. Eng
自从p53被发现以来，还没有另一种分子像PTEN一样受到如此多的关注。在发现编码10 q23上的双特异性磷酸酶肿瘤抑制因子的PTEN的5年中，已显示其为遗传性癌症综合征、Cowden综合征和几种发育障碍的易感基因;已显示其在正常鼠和人发育中起显著作用;并且已经显示其在细胞周期停滞、凋亡和/或可能的细胞迁移和细胞骨架事件中起作用。对癌细胞系的初步研究表明，PTEN引起每一种类型的癌症，因为据报道，相对高频率的各种癌细胞系，无论是来自实体瘤还是血液恶性肿瘤，都有涉及PTEN的纯合或复合杂合遗传改变。这些数据，连同生殖系人类和小鼠模型数据，表明PTEN突变发生在散发性肿瘤发生的“早期”。然而，随后在非培养的原发性肿瘤中的艰苦工作和在过去4年中仔细的体外过表达研究表明，PTEN失活的机制可以是多种多样的，并且可能是细胞类型依赖性的。此外，除了散发性子宫内膜癌，非培养散发性肿瘤中的PTEN改变可能发生“晚”，促进进展和转移。Davies等人的文章（Clin Cancer Res.，8：1904-1914，2002）在报告来自“三重威胁”战略的数据时阐明了所有这些问题，即，在体外、体内和离体，以证明腺病毒将PTEN感染到PTEN缺失PC 3前列腺癌细胞系中导致转移潜能降低，而不显著改变肿瘤大小，其主要机制是G（1）细胞周期停滞而不是细胞凋亡。
Not since the discovery of p53 has another molecule received as much attention as PTEN. In the 5 years since the discovery of PTEN, encoding a dual specificity phosphatase tumor suppressor on 10q23, it has been shown to be a susceptibility gene for an inherited cancer syndrome, Cowden syndrome, and for several developmental disorders; it has been shown to play a prominent role in normal murine and human development; and it has been shown to be instrumental in cell cycle arrest, apoptosis, and/or possibly cell migration and cytoskeletal affairs. Initial work on cancer cell lines had suggested that PTEN caused every type of cancer because it was reported that a relatively high frequency of a variety of cancer cell lines, whether derived from solid tumors or hematological malignancies, had homozygous or compound heterozygous genetic alterations involving PTEN. Such data, together with the germ-line human and murine model data, suggested that PTEN mutations occurred "early" in sporadic tumorigenesis. However, subsequent painstaking work in noncultured primary tumors and in careful in vitro overexpression studies over the last 4 years demonstrated that the mechanism of PTEN inactivation can be varied and might be cell type dependent. Furthermore, apart from sporadic endometrial carcinoma, PTEN alteration in noncultured sporadic neoplasias likely occurs "late," promoting progression and metastasis. The article by Davies et al. (Clin Cancer Res., 8: 1904-1914, 2002) sheds light on all of these issues when they report on data that derive from a "triple threat" strategy, i.e., in vitro, in vivo, and ex vivo, to demonstrate that adenoviral infection of PTEN into PTEN-null PC3 prostate cancer cell lines results in decreased metastatic potential without significantly altering tumor size via the predominant mechanism of G(1) cell cycle arrest but not apoptosis.