This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sansal, I. Articles by Sellers, W. R. Search for Related Content PubMed PubMed Citation Articles by Sansal, I. Articles by Sellers, W. R. Social Bookmarking                            What's this?

The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway

From the Department of Medical Oncology, Dana-Farber Cancer Institute; and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Address reprint requests to William R. Sellers, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 44 Binney St, Boston, MA 02115; e-mail: william_sellers{at}dfci.harvard.edu

Genetic alterations targeting the PTEN tumor suppressor gene are among the most frequently noted somatic mutations in human cancers. Such lesions have been noted in cancers of the prostate and endometrium and in glioblastoma multiforme, among many others. Moreover, germline mutation of PTEN leads to the development of the related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan-Zonana syndrome, wherein breast and thyroid cancer incidence is elevated. The protein product, PTEN, is a lipid phosphatase, the enzymatic activity of which primarily serves to remove phosphate groups from key intracellular phosphoinositide signaling molecules. This activity normally serves to restrict growth and survival signals by limiting activity of the phosphoinositide-3 kinase (PI3K) pathway. Multiple lines of evidence support the notion that this function is critical to the ability of PTEN to maintain cell homeostasis. Indeed, the absence of functional PTEN in cancer cells leads to constitutive activation of downstream components of the PI3K pathway including the Akt and mTOR kinases. In model organisms, inactivation of these kinases can reverse the effects of PTEN loss. These data raise the possibility that drugs targeting these kinases, or PI3K itself, might have significant therapeutic activity in PTEN-null cancers. Akt kinase inhibitors are still in development; however, as a first test of this hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin and rapamycin analogs are underway.

Supported by National Cancer Institute grants RO1CA85912, PO1CA89021, U01CA84995, and P50CA09038; CaP CURE (W.R.S.); the Damon Runyon Cancer Research Foundation; the Dana-Farber/Novartis Drug Discovery Program; and the Department of Defense Prostate Cancer Research Program grant DAMD17-02-1-0048 (I.S.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. Liu, P. Hou, Z. Liu, G. Wu, and M. Xing Genetic Alterations in the Phosphoinositide 3-Kinase/Akt Signaling Pathway Confer Sensitivity of Thyroid Cancer Cells to Therapeutic Targeting of Akt and Mammalian Target of Rapamycin Cancer Res., September 15, 2009; 69(18): 7311 - 7319. [Abstract] [Full Text] [PDF]

				P. Massoner, D. Colleselli, A. Matscheski, H. Pircher, S. Geley, P. Jansen Durr, and H. Klocker Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility Endocr. Relat. Cancer, September 1, 2009; 16(3): 795 - 808. [Abstract] [Full Text] [PDF]

				H.-Y. Fan, Z. Liu, M. Paquet, J. Wang, J. P. Lydon, F. J. DeMayo, and J. S. Richards Cell Type-Specific Targeted Mutations of Kras and Pten Document Proliferation Arrest in Granulosa Cells versus Oncogenic Insult to Ovarian Surface Epithelial Cells Cancer Res., August 15, 2009; 69(16): 6463 - 6472. [Abstract] [Full Text] [PDF]

				I. Rodriguez-Escudero, A. Andres-Pons, R. Pulido, M. Molina, and V. J. Cid Phosphatidylinositol 3-Kinase-dependent Activation of Mammalian Protein Kinase B/Akt in Saccharomyces cerevisiae, an in Vivo Model for the Functional Study of Akt Mutations J. Biol. Chem., May 15, 2009; 284(20): 13373 - 13383. [Abstract] [Full Text] [PDF]

				S M Khoshnaw, A R Green, D G Powe, and I O Ellis MicroRNA involvement in the pathogenesis and management of breast cancer J. Clin. Pathol., May 1, 2009; 62(5): 422 - 428. [Abstract] [Full Text] [PDF]

				M. L. Sos, M. Koker, B. A. Weir, S. Heynck, R. Rabinovsky, T. Zander, J. M. Seeger, J. Weiss, F. Fischer, P. Frommolt, et al. PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR Cancer Res., April 15, 2009; 69(8): 3256 - 3261. [Abstract] [Full Text] [PDF]

				R. Hino, H. Uozaki, N. Murakami, T. Ushiku, A. Shinozaki, S. Ishikawa, T. Morikawa, T. Nakaya, T. Sakatani, K. Takada, et al. Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma Cancer Res., April 1, 2009; 69(7): 2766 - 2774. [Abstract] [Full Text] [PDF]

				M. A.T. Hildebrandt, H. Yang, M.-C. Hung, J. G. Izzo, M. Huang, J. Lin, J. A. Ajani, and X. Wu Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy J. Clin. Oncol., February 20, 2009; 27(6): 857 - 871. [Abstract] [Full Text] [PDF]

				K. Gosselin, E. Deruy, S. Martien, C. Vercamer, F. Bouali, T. Dujardin, C. Slomianny, L. Houel-Renault, F. Chelli, Y. De Launoit, et al. Senescent Keratinocytes Die by Autophagic Programmed Cell Death Am. J. Pathol., February 1, 2009; 174(2): 423 - 435. [Abstract] [Full Text] [PDF]

				N. T. Ihle and G. Powis Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy Mol. Cancer Ther., January 1, 2009; 8(1): 1 - 9. [Abstract] [Full Text] [PDF]

				C. M.-E. Sauvageot, J. L. Weatherbee, S. Kesari, S. E. Winters, J. Barnes, J. Dellagatta, N. R. Ramakrishna, C. D. Stiles, A. L.-J. Kung, M. W. Kieran, et al. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells Neuro-oncol, January 1, 2009; 11(2): 109 - 121. [Abstract] [Full Text] [PDF]

				Y. Fu, S. Wey, M. Wang, R. Ye, C.-P. Liao, P. Roy-Burman, and A. S. Lee Pten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium PNAS, December 9, 2008; 105(49): 19444 - 19449. [Abstract] [Full Text] [PDF]

				A. Bianchini, M. Loiarro, P. Bielli, R. Busa, M. P. Paronetto, F. Loreni, R. Geremia, and C. Sette Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells Carcinogenesis, December 1, 2008; 29(12): 2279 - 2288. [Abstract] [Full Text] [PDF]

				N. Vereshchagina, M.-C. Ramel, E. Bitoun, and C. Wilson The protein phosphatase PP2A-B' subunit Widerborst is a negative regulator of cytoplasmic activated Akt and lipid metabolism in Drosophila J. Cell Sci., October 15, 2008; 121(20): 3383 - 3392. [Abstract] [Full Text] [PDF]

				M. E. Hegi, L. Liu, J. G. Herman, R. Stupp, W. Wick, M. Weller, M. P. Mehta, and M. R. Gilbert Correlation of O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation With Clinical Outcomes in Glioblastoma and Clinical Strategies to Modulate MGMT Activity J. Clin. Oncol., September 1, 2008; 26(25): 4189 - 4199. [Abstract] [Full Text] [PDF]

				N. J. Oviedo, B. J. Pearson, M. Levin, and A. Sanchez Alvarado Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling Dis. Model. Mech., September 1, 2008; 1(2-3): 131 - 143. [Abstract] [Full Text] [PDF]

				H.-Y. Fan, Z. Liu, N. Cahill, and J. S. Richards Targeted Disruption of Pten in Ovarian Granulosa Cells Enhances Ovulation and Extends the Life Span of Luteal Cells Mol. Endocrinol., September 1, 2008; 22(9): 2128 - 2140. [Abstract] [Full Text] [PDF]

				B. Hallgrimsson and D. E. Lieberman Mouse models and the evolutionary developmental biology of the skull Integr. Comp. Biol., September 1, 2008; 48(3): 373 - 384. [Abstract] [Full Text] [PDF]

				D. C. Allain Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology J. Mol. Diagn., September 1, 2008; 10(5): 383 - 395. [Abstract] [Full Text] [PDF]

				S. Frohling and H. Dohner Chromosomal Abnormalities in Cancer N. Engl. J. Med., August 14, 2008; 359(7): 722 - 734. [Full Text] [PDF]

				Z. Liu, P. Hou, M. Ji, H. Guan, K. Studeman, K. Jensen, V. Vasko, A. K. El-Naggar, and M. Xing Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Pathways in Anaplastic and Follicular Thyroid Cancers J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3106 - 3116. [Abstract] [Full Text] [PDF]

				S. E. Plon, M. L. Pirics, J. Nuchtern, J. Hicks, H. Russell, S. Agrawal, K. Zbuk, C. Eng, M. Hegde, and E. L.-H. Chin Multiple Tumors in a Child with Germ-Line Mutations in TP53 and PTEN N. Engl. J. Med., July 31, 2008; 359(5): 537 - 539. [Full Text] [PDF]

				J. V. Lacey Jr., G. L. Mutter, B. M. Ronnett, O. B. Ioffe, M. A. Duggan, B. B. Rush, A. G. Glass, D. A. Richesson, N. Chatterjee, B. Langholz, et al. PTEN Expression in Endometrial Biopsies as a Marker of Progression to Endometrial Carcinoma Cancer Res., July 15, 2008; 68(14): 6014 - 6020. [Abstract] [Full Text] [PDF]

				S. Han, J. D. Ritzenthaler, Y. Zheng, and J. Roman PPAR{beta}/{delta} agonist stimulates human lung carcinoma cell growth through inhibition of PTEN expression: the involvement of PI3K and NF-{kappa}B signals Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1238 - L1249. [Abstract] [Full Text] [PDF]

				C.-J. Chang, D. J. Mulholland, B. Valamehr, S. Mosessian, W. R. Sellers, and H. Wu PTEN Nuclear Localization Is Regulated by Oxidative Stress and Mediates p53-Dependent Tumor Suppression Mol. Cell. Biol., May 15, 2008; 28(10): 3281 - 3289. [Abstract] [Full Text] [PDF]

				N. Dey, H. E. Crosswell, P. De, R. Parsons, Q. Peng, J. D. Su, and D. L. Durden The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration Cancer Res., March 15, 2008; 68(6): 1862 - 1871. [Abstract] [Full Text] [PDF]

				A. A. Brandes, E. Franceschi, A. Tosoni, M. E. Hegi, and R. Stupp Epidermal Growth Factor Receptor Inhibitors in Neuro-oncology: Hopes and Disappointments Clin. Cancer Res., February 15, 2008; 14(4): 957 - 960. [Abstract] [Full Text] [PDF]

				C. J. Rosen Circulating IGF-I and Bone Remodeling: New Insights into Old Questions IBMS BoneKEy, January 1, 2008; 5(1): 7 - 15. [Abstract] [Full Text] [PDF]

				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 The Structure of a Human p110{alpha}/p85{alpha} Complex Elucidates the Effects of Oncogenic PI3K{alpha} Mutations Science, December 14, 2007; 318(5857): 1744 - 1748. [Abstract] [Full Text] [PDF]

				T. Tamguney and D. Stokoe New insights into PTEN J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079. [Abstract] [Full Text] [PDF]

				F. Furuya, C. Lu, M. C. Willingham, and S.-y. Cheng Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer Carcinogenesis, December 1, 2007; 28(12): 2451 - 2458. [Abstract] [Full Text] [PDF]

				J. Shao, M.K. Washington, R. Saxena, and H. Sheng Heterozygous disruption of the PTEN promotes intestinal neoplasia in APCmin/+ mouse: roles of osteopontin Carcinogenesis, December 1, 2007; 28(12): 2476 - 2483. [Abstract] [Full Text] [PDF]

				K. M. Vasudevan, R. Burikhanov, A. Goswami, and V. M. Rangnekar Suppression of PTEN Expression Is Essential for Antiapoptosis and Cellular Transformation by Oncogenic Ras Cancer Res., November 1, 2007; 67(21): 10343 - 10350. [Abstract] [Full Text] [PDF]

				A. Andres-Pons, I. Rodriguez-Escudero, A. Gil, A. Blanco, A. Vega, M. Molina, R. Pulido, and V. J. Cid In vivo Functional Analysis of the Counterbalance of Hyperactive Phosphatidylinositol 3-Kinase p110 Catalytic Oncoproteins by the Tumor Suppressor PTEN Cancer Res., October 15, 2007; 67(20): 9731 - 9739. [Abstract] [Full Text] [PDF]

				G. Maeda, T. Chiba, S. Kawashiri, T. Satoh, and K. Imai Epigenetic Inactivation of I{kappa}B Kinase-{alpha} in Oral Carcinomas and Tumor Progression Clin. Cancer Res., September 1, 2007; 13(17): 5041 - 5047. [Abstract] [Full Text] [PDF]

				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 The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management J. Med. Genet., September 1, 2007; 44(9): 594 - 602. [Abstract] [Full Text] [PDF]

				D. G. McEwan, V. G. Brunton, G. S. Baillie, N. R. Leslie, M. D. Houslay, and M. C. Frame Chemoresistant KM12C Colon Cancer Cells Are Addicted to Low Cyclic AMP Levels in a Phosphodiesterase 4-Regulated Compartment via Effects on Phosphoinositide 3-Kinase Cancer Res., June 1, 2007; 67(11): 5248 - 5257. [Abstract] [Full Text] [PDF]

				Y. Wang, P. Hou, H. Yu, W. Wang, M. Ji, S. Zhao, S. Yan, X. Sun, D. Liu, B. Shi, et al. High Prevalence and Mutual Exclusivity of Genetic Alterations in the Phosphatidylinositol-3-Kinase/Akt Pathway in Thyroid Tumors J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2387 - 2390. [Abstract] [Full Text] [PDF]

				Z. Yu, P. M. Weinberger, C. Sasaki, B. L. Egleston, W. F. Speier IV, B. Haffty, D. Kowalski, R. Camp, D. Rimm, E. Vairaktaris, et al. Phosphorylation of Akt (Ser473) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2007; 16(3): 553 - 558. [Abstract] [Full Text] [PDF]

				C.-A. O. Nathan, N. Amirghahari, X. Rong, T. Giordano, D. Sibley, M. Nordberg, J. Glass, A. Agarwal, and G. Caldito Mammalian Target of Rapamycin Inhibitors as Possible Adjuvant Therapy for Microscopic Residual Disease in Head and Neck Squamous Cell Cancer Cancer Res., March 1, 2007; 67(5): 2160 - 2168. [Abstract] [Full Text] [PDF]

				Y. Fujiwara, Y. Hosokawa, K. Watanabe, S. Tanimura, K.-i. Ozaki, and M. Kohno Blockade of the phosphatidylinositol-3-kinase-Akt signaling pathway enhances the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the pathway is constitutively activated Mol. Cancer Ther., March 1, 2007; 6(3): 1133 - 1142. [Abstract] [Full Text] [PDF]

				P. Hou, D. Liu, Y. Shan, S. Hu, K. Studeman, S. Condouris, Y. Wang, A. Trink, A. K. El-Naggar, G. Tallini, et al. Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer Clin. Cancer Res., February 15, 2007; 13(4): 1161 - 1170. [Abstract] [Full Text] [PDF]

				S. R. Choudhari, M. A. Khan, G. Harris, D. Picker, G. S. Jacob, T. Block, and K. Shailubhai Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent, Atiprimod Mol. Cancer Ther., January 1, 2007; 6(1): 112 - 121. [Abstract] [Full Text] [PDF]

				A. Yacoub, W. Hawkins, D. Hanna, H. Young, M. A. Park, M. Grant, J. D. Roberts, D. T. Curiel, P. B. Fisher, K. Valerie, et al. Human Chorionic Gonadotropin Modulates Prostate Cancer Cell Survival after Irradiation or HMG CoA Reductase Inhibitor Treatment Mol. Pharmacol., January 1, 2007; 71(1): 259 - 275. [Abstract] [Full Text] [PDF]

				T. Inoue, T. Yoshida, Y. Shimizu, T. Kobayashi, T. Yamasaki, Y. Toda, T. Segawa, T. Kamoto, E. Nakamura, and O. Ogawa Requirement of Androgen-Dependent Activation of Protein Kinase C{zeta} for Androgen-Dependent Cell Proliferation in LNCaP Cells and Its Roles in Transition to Androgen-Independent Cells Mol. Endocrinol., December 1, 2006; 20(12): 3053 - 3069. [Abstract] [Full Text] [PDF]

				A. Gil, A. Andres-Pons, E. Fernandez, M. Valiente, J. Torres, J. Cervera, and R. Pulido Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs Mol. Biol. Cell, September 1, 2006; 17(9): 4002 - 4013. [Abstract] [Full Text] [PDF]

				S. Xia, Y. Lu, J. Wang, C. He, S. Hong, C. N. Serhan, and J. X. Kang Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids PNAS, August 15, 2006; 103(33): 12499 - 12504. [Abstract] [Full Text] [PDF]

				H.-G. Wendel, A. Malina, Z. Zhao, L. Zender, S. C. Kogan, C. Cordon-Cardo, J. Pelletier, and S. W. Lowe Determinants of Sensitivity and Resistance to Rapamycin-Chemotherapy Drug Combinations In vivo. Cancer Res., August 1, 2006; 66(15): 7639 - 7646. [Abstract] [Full Text] [PDF]

				N. Pore, Z. Jiang, H.-K. Shu, E. Bernhard, G. D. Kao, and A. Maity Akt1 Activation Can Augment Hypoxia-Inducible Factor-1{alpha} Expression by Increasing Protein Translation through a Mammalian Target of Rapamycin-Independent Pathway Mol. Cancer Res., July 1, 2006; 4(7): 471 - 479. [Abstract] [Full Text] [PDF]

				C. W. Rinker-Schaeffer, J. P. O'Keefe, D. R. Welch, and D. Theodorescu Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application. Clin. Cancer Res., July 1, 2006; 12(13): 3882 - 3889. [Full Text] [PDF]

				M.-L. Chen, P.-Z. Xu, X. Peng, W. S. Chen, G. Guzman, X. Yang, A. Di Cristofano, P. P. Pandolfi, and N. Hay The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Genes & Dev., June 15, 2006; 20(12): 1569 - 1574. [Abstract] [Full Text] [PDF]

				G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al. Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697. [Abstract] [Full Text] [PDF]

				P. R. Cutillas, A. Khwaja, M. Graupera, W. Pearce, S. Gharbi, M. Waterfield, and B. Vanhaesebroeck Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometry PNAS, June 13, 2006; 103(24): 8959 - 8964. [Abstract] [Full Text] [PDF]

				C. A. Haiman, D. O. Stram, I. Cheng, E. E. Giorgi, L. Pooler, K. Penney, L. Le Marchand, B. E. Henderson, and M. L. Freedman Common Genetic Variation at PTEN and Risk of Sporadic Breast and Prostate Cancer. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 1021 - 1025. [Abstract] [Full Text] [PDF]

				J. V. Schaffer, H. Kamino, A. Witkiewicz, J. M. McNiff, and S. J. Orlow Mucocutaneous Neuromas: An Underrecognized Manifestation of PTEN Hamartoma-Tumor Syndrome. Arch Dermatol, May 1, 2006; 142(5): 625 - 632. [Abstract] [Full Text] [PDF]

				S.-W. Han, T.-Y. Kim, Y. K. Jeon, P. G. Hwang, S.-A. Im, K.-H. Lee, J. H. Kim, D.-W. Kim, D. S. Heo, N. K. Kim, et al. Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation Clin. Cancer Res., April 15, 2006; 12(8): 2538 - 2544. [Abstract] [Full Text] [PDF]

				L. I. Yoo, D. W. Liu, S. L. Vu, R. T. Bronson, H. Wu, and J. Yuan Pten Deficiency Activates Distinct Downstream Signaling Pathways in a Tissue-Specific Manner Cancer Res., February 15, 2006; 66(4): 1929 - 1939. [Abstract] [Full Text] [PDF]

				F. Furuya, J. A. Hanover, and S.-y. Cheng Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone beta receptor PNAS, February 7, 2006; 103(6): 1780 - 1785. [Abstract] [Full Text] [PDF]

				F. Kaper, N. Dornhoefer, and A. J. Giaccia Mutations in the PI3K/PTEN/TSC2 Pathway Contribute to Mammalian Target of Rapamycin Activity and Increased Translation under Hypoxic Conditions Cancer Res., February 1, 2006; 66(3): 1561 - 1569. [Abstract] [Full Text] [PDF]

				B. Davidson, V. Espina, S. M. Steinberg, V. A. Florenes, L. A. Liotta, G. B. Kristensen, C. G. Trope, A. Berner, and E. C. Kohn Proteomic Analysis of Malignant Ovarian Cancer Effusions as a Tool for Biologic and Prognostic Profiling Clin. Cancer Res., February 1, 2006; 12(3): 791 - 799. [Abstract] [Full Text] [PDF]

				J. J. Zhao, Z. Liu, L. Wang, E. Shin, M. F. Loda, and T. M. Roberts The oncogenic properties of mutant p110{alpha} and p110{beta} phosphatidylinositol 3-kinases in human mammary epithelial cells PNAS, December 20, 2005; 102(51): 18443 - 18448. [Abstract] [Full Text] [PDF]

				S. J. Isakoff, J. A. Engelman, H. Y. Irie, J. Luo, S. M. Brachmann, R. V. Pearline, L. C. Cantley, and J. S. Brugge Breast Cancer-Associated PIK3CA Mutations Are Oncogenic in Mammary Epithelial Cells Cancer Res., December 1, 2005; 65(23): 10992 - 11000. [Abstract] [Full Text] [PDF]

				T. Dutu, S. Michiels, P. Fouret, F. Penault-Llorca, P. Validire, S. Benhamou, E. Taranchon, L. Morat, D. Grunenwald, T. Le Chevalier, et al. Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers Ann. Onc., December 1, 2005; 16(12): 1906 - 1914. [Abstract] [Full Text] [PDF]

				G. Garcia-Rostan, A. M. Costa, I. Pereira-Castro, G. Salvatore, R. Hernandez, M. J.A. Hermsem, A. Herrero, A. Fusco, J. Cameselle-Teijeiro, and M. Santoro Mutation of the PIK3CA Gene in Anaplastic Thyroid Cancer Cancer Res., November 15, 2005; 65(22): 10199 - 10207. [Abstract] [Full Text] [PDF]

				A J Bauer and C A Stratakis The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis J. Med. Genet., November 1, 2005; 42(11): 801 - 810. [Abstract] [Full Text] [PDF]

				A. Petit, T. Kawarai, E. Paitel, N. Sanjo, M. Maj, M. Scheid, F. Chen, Y. Gu, H. Hasegawa, S. Salehi-Rad, et al. Wild-type PINK1 Prevents Basal and Induced Neuronal Apoptosis, a Protective Effect Abrogated by Parkinson Disease-related Mutations J. Biol. Chem., October 7, 2005; 280(40): 34025 - 34032. [Abstract] [Full Text] [PDF]

				S. Han, J. D. Ritzenthaler, B. Wingerd, and J. Roman Activation of Peroxisome Proliferator-activated Receptor {beta}/{delta} (PPAR{beta}/{delta}) Increases the Expression of Prostaglandin E2 Receptor Subtype EP4: THE ROLES OF PHOSPHATIDYLINOSITOL 3-KINASE AND CCAAT/ENHANCER-BINDING PROTEIN {beta} J. Biol. Chem., September 30, 2005; 280(39): 33240 - 33249. [Abstract] [Full Text] [PDF]

				L. Chen, S. Meng, H. Wang, P. Bali, W. Bai, B. Li, P. Atadja, K. N. Bhalla, and J. Wu Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824 Mol. Cancer Ther., September 1, 2005; 4(9): 1311 - 1319. [Abstract] [Full Text] [PDF]

				S.-Y. Sun, L. M. Rosenberg, X. Wang, Z. Zhou, P. Yue, H. Fu, and F. R. Khuri Activation of Akt and eIF4E Survival Pathways by Rapamycin-Mediated Mammalian Target of Rapamycin Inhibition Cancer Res., August 15, 2005; 65(16): 7052 - 7058. [Abstract] [Full Text] [PDF]

				J. R. Graff, A. M. McNulty, K. R. Hanna, B. W. Konicek, R. L. Lynch, S. N. Bailey, C. Banks, A. Capen, R. Goode, J. E. Lewis, et al. The Protein Kinase C{beta}-Selective Inhibitor, Enzastaurin (LY317615.HCl), Suppresses Signaling through the AKT Pathway, Induces Apoptosis, and Suppresses Growth of Human Colon Cancer and Glioblastoma Xenografts Cancer Res., August 15, 2005; 65(16): 7462 - 7469. [Abstract] [Full Text] [PDF]

				J. Luo, C. L. Sobkiw, N. M. Logsdon, J. M. Watt, S. Signoretti, F. O'Connell, E. Shin, Y. Shim, L. Pao, B. G. Neel, et al. Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase PNAS, July 19, 2005; 102(29): 10238 - 10243. [Abstract] [Full Text] [PDF]

				R. J. Phillips, J. Mestas, M. Gharaee-Kermani, M. D. Burdick, A. Sica, J. A. Belperio, M. P. Keane, and R. M. Strieter Epidermal Growth Factor and Hypoxia-induced Expression of CXC Chemokine Receptor 4 on Non-small Cell Lung Cancer Cells Is Regulated by the Phosphatidylinositol 3-Kinase/PTEN/AKT/Mammalian Target of Rapamycin Signaling Pathway and Activation of Hypoxia Inducible Factor-1{alpha} J. Biol. Chem., June 10, 2005; 280(23): 22473 - 22481. [Abstract] [Full Text] [PDF]

				P. S. Hammerman, C. J. Fox, M. J. Birnbaum, and C. B. Thompson Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival Blood, June 1, 2005; 105(11): 4477 - 4483. [Abstract] [Full Text] [PDF]

				R. I. Feldman, J. M. Wu, M. A. Polokoff, M. J. Kochanny, H. Dinter, D. Zhu, S. L. Biroc, B. Alicke, J. Bryant, S. Yuan, et al. Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1 J. Biol. Chem., May 20, 2005; 280(20): 19867 - 19874. [Abstract] [Full Text] [PDF]

				B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Neuro-oncol, April 1, 2005; 7(2): 134 - 153. [Abstract] [PDF]

				E. A. Sausville Indifferently Pursued or Unowned Drugs: Who Should Lead Where Companies Do Not Tread? J. Clin. Oncol., March 20, 2005; 23(9): 1796 - 1798. [Full Text] [PDF]

				D. F. Stern More than a Marker... Phosphorylated Akt in Prostate Carcinoma Clin. Cancer Res., October 1, 2004; 10(19): 6407 - 6410. [Full Text] [PDF]