PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
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DOI：
10.1126/science.275.5308.1943
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发表时间：
1997-03-28
期刊：
影响因子：
56.9
通讯作者：
Parsons, R
中科院分区：
文献类型：
--
作者：
Li, J;Yen, C;Parsons, R
通过对人类染色体 10q23 上的纯合缺失进行定位，分离出了候选肿瘤抑制基因 PTEN，该基因似乎在人类癌症中以相当高的频率发生突变。在初步筛选中，在 31% (13/42) 的胶质母细胞瘤细胞系和异种移植物、100% (4/4) 的前列腺癌细胞系、6% (4/65) 的乳腺癌细胞系和异种移植物以及 17% (3/18) 的原发性胶质母细胞瘤中检测到 PTEN 突变。预测的 PTEN 产物具有蛋白质酪氨酸磷酸酶结构域，并且与张力蛋白具有广泛的同源性，张力蛋白是一种与粘着斑处的肌动蛋白丝相互作用的蛋白质。这些同源性表明 PTEN 可能通过拮抗蛋白酪氨酸激酶来抑制肿瘤细胞生长，并可能通过粘着斑相互作用调节肿瘤细胞侵袭和转移。
Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.