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.
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We thank B. Vogelstein, N. Tonks, and E. Marcantonio for their comments and S. Kalachikov and R. Hauptschein for helpful suggestions. R.P. is a James S. McDonnell Scholar. M.H.W. is an American Cancer Society Research Professor and is supported by the Department of the Army (DAMD 17-94-I4247), NCI (5R35 CA39829), Amplicon Corporation, and the “1 in 9” breast cancer organization. This work is dedicated to the memory of Richard K. Parsons and Richard P. Sanchez.
Volume 275 | Issue 5308
28 March 1997
28 March 1997
© 1997 American Association for the Advancement of Science.
Received: 3 February 1997
Accepted: 27 February 1997
Published in print: 28 March 1997
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