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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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Phosphoinositide Binding to the Substrate Regulates Susceptibility to Proteolysis by Calpain.
C. R. Sprague, T. S. Fraley, H. S. Jang, S. Lal, and J. A. Greenwood (2008)
J. Biol. Chem. 283, 9217-9223
   Abstract »    Full Text »    PDF »
Phosphatase and Tensin Homologue Deleted on Chromosome 10 Deficiency Accelerates Tumor Induction in a Mouse Model of ErbB-2 Mammary Tumorigenesis.
N. Dourdin, B. Schade, R. Lesurf, M. Hallett, R. J. Munn, R. D. Cardiff, and W. J. Muller (2008)
Cancer Res. 68, 2122-2131
   Abstract »    Full Text »    PDF »
SnoRNA U50 is a candidate tumor-suppressor gene at 6q14.3 with a mutation associated with clinically significant prostate cancer.
X.-Y. Dong, C. Rodriguez, P. Guo, X. Sun, J. T. Talbot, W. Zhou, J. Petros, Q. Li, R. L. Vessella, A. S. Kibel, et al. (2008)
Hum. Mol. Genet. 17, 1031-1042
   Abstract »    Full Text »    PDF »
The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration.
N. Dey, H. E. Crosswell, P. De, R. Parsons, Q. Peng, J. D. Su, and D. L. Durden (2008)
Cancer Res. 68, 1862-1871
   Abstract »    Full Text »    PDF »
Phase II Study of Predictive Biomarker Profiles for Response Targeting Human Epidermal Growth Factor Receptor 2 (HER-2) in Advanced Inflammatory Breast Cancer With Lapatinib Monotherapy.
S. Johnston, M. Trudeau, B. Kaufman, H. Boussen, K. Blackwell, P. LoRusso, D. P. Lombardi, S. Ben Ahmed, D. L. Citrin, M. L. DeSilvio, et al. (2008)
J. Clin. Oncol. 26, 1066-1072
   Abstract »    Full Text »    PDF »
Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice.
Y. Takei, Y. Saga, H. Mizukami, T. Takayama, M. Ohwada, K. Ozawa, and M. Suzuki (2008)
Mol. Cancer Ther. 7, 704-711
   Abstract »    Full Text »    PDF »
Heterozygous Screen in Saccharomyces cerevisiae Identifies Dosage-Sensitive Genes That Affect Chromosome Stability.
E. D. Strome, X. Wu, M. Kimmel, and S. E. Plon (2008)
Genetics 178, 1193-1207
   Abstract »    Full Text »    PDF »
PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a).
B. M. Emerling, F. Weinberg, J.-L. Liu, T. W. Mak, and N. S. Chandel (2008)
PNAS 105, 2622-2627
   Abstract »    Full Text »    PDF »
Temporally controlled ablation of PTEN in adult mouse prostate epithelium generates a model of invasive prostatic adenocarcinoma.
C. K. Ratnacaram, M. Teletin, M. Jiang, X. Meng, P. Chambon, and D. Metzger (2008)
PNAS 105, 2521-2526
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Pten Inactivation Accelerates Oncogenic K-ras-Initiated Tumorigenesis in a Mouse Model of Lung Cancer.
K. Iwanaga, Y. Yang, M. G. Raso, L. Ma, A. E. Hanna, N. Thilaganathan, S. Moghaddam, C. M. Evans, H. Li, W.-W. Cai, et al. (2008)
Cancer Res. 68, 1119-1127
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Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway.
N. de la Iglesia, G. Konopka, S. V. Puram, J. A. Chan, R. M. Bachoo, M. J. You, D. E. Levy, R. A. DePinho, and A. Bonni (2008)
Genes & Dev. 22, 449-462
   Abstract »    Full Text »    PDF »
Translation of Genetic Discoveries into Clinical Therapies.
D. G. Hackam and A. S. Hackam (2008)
Ann Intern Med 148, 246-247
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c-Met Inhibitors with Novel Binding Mode Show Activity against Several Hereditary Papillary Renal Cell Carcinoma-related Mutations.
S. F. Bellon, P. Kaplan-Lefko, Y. Yang, Y. Zhang, J. Moriguchi, K. Rex, C. W. Johnson, P. E. Rose, A. M. Long, A. B. O'Connor, et al. (2008)
J. Biol. Chem. 283, 2675-2683
   Abstract »    Full Text »    PDF »
Transduction of Phosphatase and Tensin Homolog Deleted on Chromosome 10 into Eosinophils Attenuates Survival, Chemotaxis, and Airway Inflammation.
T. Adachi, S. Hanaka, T. Masuda, H. Yoshihara, H. Nagase, and K. Ohta (2007)
J. Immunol. 179, 8105-8111
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Pharmacodynamic Markers of Perifosine Efficacy.
B. T. Hennessy, Y. Lu, E. Poradosu, Q. Yu, S. Yu, H. Hall, M. S. Carey, M. Ravoori, A. M. Gonzalez-Angulo, R. Birch, et al. (2007)
Clin. Cancer Res. 13, 7421-7431
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The Structure of a Human p110{alpha}/p85{alpha} Complex Elucidates the Effects of Oncogenic PI3K{alpha} Mutations.
C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, and L. M. Amzel (2007)
Science 318, 1744-1748
   Abstract »    Full Text »    PDF »
New insights into PTEN.
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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 »


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