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PTEN是一种假定的蛋白酪氨酸磷酸酶基因,在人类脑癌、乳腺癌和前列腺癌中发生突变。

PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.

作者信息

Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S I, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner S H, Giovanella B C, Ittmann M, Tycko B, Hibshoosh H, Wigler M H, Parsons R

机构信息

Department of Pathology, College of Physicians & Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.

出版信息

Science. 1997 Mar 28;275(5308):1943-7. doi: 10.1126/science.275.5308.1943.

Abstract

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.

摘要

对人类10号染色体q23区域纯合缺失的定位研究,导致了一个候选肿瘤抑制基因PTEN的分离,该基因在人类癌症中似乎有相当高的突变频率。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瘤、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瘤以及17%(3/18)的原发性胶质母细胞瘤中检测到PTEN突变。预测的PTEN产物具有一个蛋白酪氨酸磷酸酶结构域,并且与张力蛋白有广泛的同源性,张力蛋白是一种在粘着斑处与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,并可能通过在粘着斑处的相互作用来调节肿瘤细胞的侵袭和转移。

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