Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Nat Rev Cancer. 2011 Apr;11(4):289-301. doi: 10.1038/nrc3037.
PTEN is among the most frequently inactivated tumour suppressor genes in sporadic cancer. PTEN has dual protein and lipid phosphatase activity, and its tumour suppressor activity is dependent on its lipid phosphatase activity, which negatively regulates the PI3K-AKT-mTOR pathway. Germline mutations in PTEN have been described in a variety of rare syndromes that are collectively known as the PTEN hamartoma tumour syndromes (PHTS). Cowden syndrome is the best-described syndrome within PHTS, with approximately 80% of patients having germline PTEN mutations. Patients with Cowden syndrome have an increased incidence of cancers of the breast, thyroid and endometrium, which correspond to sporadic tumour types that commonly exhibit somatic PTEN inactivation. Pten deletion in mice leads to Cowden syndrome-like phenotypes, and tissue-specific Pten deletion has provided clues to the role of PTEN mutation and loss in specific tumour types. Studying PTEN in the continuum of rare syndromes, common cancers and mouse models provides insight into the role of PTEN in tumorigenesis and will inform targeted drug development.
PTEN 是散发性癌症中最常失活的肿瘤抑制基因之一。PTEN 具有双重蛋白和脂质磷酸酶活性，其肿瘤抑制活性依赖于其脂质磷酸酶活性，后者负调控 PI3K-AKT-mTOR 通路。PTEN 的种系突变已在多种罕见综合征中描述，这些综合征统称为 PTEN 错构瘤肿瘤综合征 (PHTS)。Cowden 综合征是 PHTS 中描述最详细的综合征，约 80%的患者存在种系 PTEN 突变。Cowden 综合征患者乳腺癌、甲状腺癌和子宫内膜癌的发病率增加，这些癌症与常见的散发性肿瘤类型相对应，这些肿瘤类型通常表现出体细胞 PTEN 失活。小鼠中 Pten 的缺失导致 Cowden 综合征样表型，组织特异性 Pten 缺失为 PTEN 突变和缺失在特定肿瘤类型中的作用提供了线索。在罕见综合征、常见癌症和小鼠模型的连续体中研究 PTEN，可以深入了解 PTEN 在肿瘤发生中的作用，并为靶向药物开发提供信息。
