Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression
Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression
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DOI：
10.1073/pnas.201167798
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Ittmann, M
中科院分区：
文献类型：
--
作者：
Kwabi-Addo, B;Giri, D;Ittmann, M
PTEN基因编码一种脂质磷酸酶，其负调节磷脂酰肌醇3-激酶途径，并且在多种恶性肿瘤中失活。在前列腺癌和其他人类恶性肿瘤中，在含有人PTEN基因的10q23.3区域观察到高杂合性丢失率，但通过突变或纯合缺失导致的PTEN基因双等位基因失活率显着低于杂合性丢失率。转基因小鼠前列腺腺癌模型是一种特征性良好的前列腺癌动物模型。对与Pten（+/-）杂合小鼠交配的小鼠前列腺小鼠的转基因腺癌中前列腺癌进展的分析，以及对所得肿瘤中Pten基因和蛋白质的分析，揭示了Pten基因的单倍不足促进了该模型系统中前列腺癌的进展。这一观察结果为在前列腺癌和许多人类恶性肿瘤中观察到的10 q23杂合性丢失率和双等位基因PTEN失活率的不一致性提供了一个潜在的解释。
The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten(+/-) heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.