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Science 28 March 1997:
Vol. 275. no. 5308, pp. 1943 - 1947
DOI: 10.1126/science.275.5308.1943
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Reports

PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

Jing Li, * Clifford Yen, * Danny Liaw, * Katrina Podsypanina, * Shikha Bose, Steven I. Wang, Janusz Puc, Christa Miliaresis, Linda Rodgers, Richard McCombie, Sandra H. Bigner, Beppino C. Giovanella, Michael Ittmann, Ben Tycko, Hanina Hibshoosh, Michael H. Wigler, Ramon Parsons dagger

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.

J. Li, D. Liaw, K. Podsypanina, S. I. Wang, J. Puc, C. Miliaresis, R. Parsons, Department of Pathology and Department of Medicine, College of Physicians & Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.
C. Yen, L. Rodgers, R. McCombie, M. Wigler, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
S. H. Bigner, Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
B. Giovanella, Stehlin Foundation for Cancer Research, St. Joseph Hospital, Houston, TX 77003, USA.
M. Ittmann, New York VA Medical Center and Department of Pathology, New York University, 423 East 23 Street, New York, NY 10010, USA.
S. Bose, B. Tycko, H. Hibshoosh, Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.

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Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometry.
P. R. Cutillas, A. Khwaja, M. Graupera, W. Pearce, S. Gharbi, M. Waterfield, and B. Vanhaesebroeck (2006)
PNAS 103, 8959-8964
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Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules.
X. Zhang, F. Li, A. Bulloj, Y.-w. Zhang, G. Tong, Z. Zhang, F.-F. Liao, and H. Xu (2006)
FASEB J 20, 1272-1274
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The Phosphoinositide 3-Kinase/Akt Pathway: A New Target in Human Renal Cell Carcinoma Therapy..
C. Sourbier, V. Lindner, H. Lang, A. Agouni, E. Schordan, S. Danilin, S. Rothhut, D. Jacqmin, J.-J. Helwig, and T. Massfelder (2006)
Cancer Res. 66, 5130-5142
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Phosphatidylinositol 3'-Kinase/AKT Signaling Is Activated in Medulloblastoma Cell Proliferation and Is Associated with Reduced Expression of PTEN..
W. Hartmann, B. Digon-Sontgerath, A. Koch, A. Waha, E. Endl, I. Dani, D. Denkhaus, C. G. Goodyer, N. Sorensen, O. D. Wiestler, et al. (2006)
Clin. Cancer Res. 12, 3019-3027
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Frequent Silencing of the Candidate Tumor Suppressor PCDH20 by Epigenetic Mechanism in Non-Small-Cell Lung Cancers..
I. Imoto, H. Izumi, S. Yokoi, H. Hosoda, T. Shibata, F. Hosoda, M. Ohki, S. Hirohashi, and J. Inazawa (2006)
Cancer Res. 66, 4617-4626
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Mucocutaneous Neuromas: An Underrecognized Manifestation of PTEN Hamartoma-Tumor Syndrome..
J. V. Schaffer, H. Kamino, A. Witkiewicz, J. M. McNiff, and S. J. Orlow (2006)
Arch Dermatol 142, 625-632
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