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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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T. Tamguney and D. Stokoe (2007)
J. Cell Sci. 120, 4071-4079
   Abstract »    Full Text »    PDF »
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
L. Zhang, J. Yu, H. Pan, P. Hu, Y. Hao, W. Cai, H. Zhu, A. D. Yu, X. Xie, D. Ma, et al. (2007)
PNAS 104, 19023-19028
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Identification of a Novel Inhibitor of Differentiation-1 (ID-1) Binding Partner, Caveolin-1, and Its Role in Epithelial-Mesenchymal Transition and Resistance to Apoptosis in Prostate Cancer Cells.
X. Zhang, M.-T. Ling, Q. Wang, C.-K. Lau, S. C. L. Leung, T. K. Lee, A. L. M. Cheung, Y.-C. Wong, and X. Wang (2007)
J. Biol. Chem. 282, 33284-33294
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Cell Cycle Dependent Nuclear Export of Phosphatase and Tensin Homologue Tumor Suppressor Is Regulated by the Phosphoinositide-3-Kinase Signaling Cascade.
J.-L. Liu, Z. Mao, T. A. LaFortune, M. M. Alonso, G. E. Gallick, J. Fueyo, and W.K. A. Yung (2007)
Cancer Res. 67, 11054-11063
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Malignant astrocytic glioma: genetics, biology, and paths to treatment.
F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. (2007)
Genes & Dev. 21, 2683-2710
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RAS/ERK modulates TGF{beta}-regulated PTEN expression in human pancreatic adenocarcinoma cells.
J. Y.C. Chow, K. T. Quach, B. L. Cabrera, J. A. Cabral, S. E. Beck, and J. M. Carethers (2007)
Carcinogenesis 28, 2321-2327
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Actin cytoskeleton dynamics linked to synovial fibroblast activation as a novel pathogenic principle in TNF-driven arthritis.
Y Vasilopoulos, V Gkretsi, M Armaka, V Aidinis, and G Kollias (2007)
Ann Rheum Dis 66, iii23-iii28
   Abstract »    Full Text »    PDF »
Phase I Study of Everolimus in Pediatric Patients With Refractory Solid Tumors.
M. Fouladi, F. Laningham, J. Wu, M. A. O'Shaughnessy, K. Molina, A. Broniscer, S. L. Spunt, I. Luckett, C. F. Stewart, P. J. Houghton, et al. (2007)
J. Clin. Oncol. 25, 4806-4812
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Nerve Growth Factor Induces Endothelial Cell Invasion and Cord Formation by Promoting Matrix Metalloproteinase-2 Expression through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway and AP-2 Transcription Factor.
M.-J. Park, H.-J. Kwak, H.-C. Lee, D.-H. Yoo, I.-C. Park, M.-S. Kim, S.-H. Lee, C. H. Rhee, and S.-I. Hong (2007)
J. Biol. Chem. 282, 30485-30496
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Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies.
J. M. Stommel, A. C. Kimmelman, H. Ying, R. Nabioullin, A. H. Ponugoti, R. Wiedemeyer, A. H. Stegh, J. E. Bradner, K. L. Ligon, C. Brennan, et al. (2007)
Science 318, 287-290
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Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner.
P. Song, Y. Wu, J. Xu, Z. Xie, Y. Dong, M. Zhang, and M.-H. Zou (2007)
Circulation 116, 1585-1595
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PC-1/PrLZ Contributes to Malignant Progression in Prostate Cancer.
H. Zhang, J. Wang, B. Pang, R.-x. Liang, S. Li, P.-t. Huang, R. Wang, L. W.K. Chung, H. E. Zhau, C. Huang, et al. (2007)
Cancer Res. 67, 8906-8913
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Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B Induced Gliomagenesis.
M. Ferletta, L. Uhrbom, T. Olofsson, F. Ponten, and B. Westermark (2007)
Mol. Cancer Res. 5, 891-897
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The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management.
W.-H. Tan, H. N Baris, P. E Burrows, C. D Robson, A. I Alomari, J. B Mulliken, S. J Fishman, and M. B Irons (2007)
J. Med. Genet. 44, 594-602
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Modulation of Intracellular Signaling Pathways to Induce Apoptosis in Prostate Cancer Cells.
J. Guo, T. Zhu, Z.-X. J. Xiao, and C.-Y. Chen (2007)
J. Biol. Chem. 282, 24364-24372
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Regulation of PTEN Expression in Intestinal Epithelial Cells by c-Jun NH2-Terminal Kinase Activation and Nuclear Factor-{kappa}B Inhibition.
Q. Wang, Y. Zhou, X. Wang, D. H. Chung, and B. M. Evers (2007)
Cancer Res. 67, 7773-7781
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PTEN plays a role in the suppression of lateral pseudopod formation during Dictyostelium motility and chemotaxis.
D. Wessels, D. F. Lusche, S. Kuhl, P. Heid, and D. R. Soll (2007)
J. Cell Sci. 120, 2517-2531
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Ca2+-Permeable AMPA Receptors Regulate Growth of Human Glioblastoma via Akt Activation.
S. Ishiuchi, Y. Yoshida, K. Sugawara, M. Aihara, T. Ohtani, T. Watanabe, N. Saito, K. Tsuzuki, H. Okado, A. Miwa, et al. (2007)
J. Neurosci. 27, 7987-8001
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Phosphorylated Galectin-3 Mediates Tumor Necrosis Factor-related Apoptosis-inducing Ligand Signaling by Regulating Phosphatase and Tensin Homologue Deleted on Chromosome 10 in Human Breast Carcinoma Cells.
N. Mazurek, Y. J. Sun, K.-F. Liu, M. Z. Gilcrease, W. Schober, P. Nangia-Makker, A. Raz, and R. S. Bresalier (2007)
J. Biol. Chem. 282, 21337-21348
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Insulin-like growth factor binding protein 2 promotes glioma development and progression.
S. M. Dunlap, J. Celestino, H. Wang, R. Jiang, E. C. Holland, G. N. Fuller, and W. Zhang (2007)
PNAS 104, 11736-11741
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PTEN, more than the AKT pathway.
C. Blanco-Aparicio, O. Renner, J. F.M. Leal, and A. Carnero (2007)
Carcinogenesis 28, 1379-1386
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Determining Risk of Biochemical Recurrence in Prostate Cancer by Immunohistochemical Detection of PTEN Expression and Akt Activation.
R. Bedolla, T. J. Prihoda, J. I. Kreisberg, S. N. Malik, N. K. Krishnegowda, D. A. Troyer, and P. M. Ghosh (2007)
Clin. Cancer Res. 13, 3860-3867
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Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors.
Y. Su, F. A. Simmen, R. Xiao, and R. C. M. Simmen (2007)
Physiol Genomics 30, 8-16
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