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The roles of PTEN in development, physiology and tumorigenesis in mouse models: a tissue-by-tissue survey

Oncogene volume 27, pages 5398–5415 (2008)Cite this article

Abstract

In 1997, PTEN (phosphatase and tensin homologue deleted on chromosome 10, 10q23.3) was identified as an important tumor suppressor gene that is inactivated in a wide variety of human cancers. Ever since, PTEN's function has been extensively studied, and huge progress has been made in understanding PTEN's role in normal physiology and disease. In this review, we will systematically summarize the important data that have been gained from gene inactivation studies in mice and will put these data into physiological context using a tissue-by-tissue approach. We will cover mice exhibiting complete and constitutive inactivation of Pten as well as a large number of strains in which Pten has been conditionally deleted in specific tissues. We hope to highlight not only the tumor suppressive function of Pten but also its roles in embryogenesis and in the maintenance of the normal physiological functions of many organ systems.

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References

  • Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E et al. (2001). Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409: 729–733.

    CAS  PubMed  Google Scholar 

  • Anzelon AN, Wu H, Rickert RC . (2003). Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nat Immunol 4: 287–294.

    CAS  PubMed  Google Scholar 

  • Aveyard JS, Skilleter A, Habuchi T, Knowles MA . (1999). Somatic mutation of PTEN in bladder carcinoma. Br J Cancer 80: 904–908.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Backman S, Stambolic V, Mak T . (2002). PTEN function in mammalian cell size regulation. Curr Opin Neurobiol 12: 516–522.

    CAS  PubMed  Google Scholar 

  • Backman SA, Ghazarian D, So K, Sanchez O, Wagner KU, Hennighausen L et al. (2004). Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten. Proc Natl Acad Sci USA 101: 1725–1730.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J et al. (2001). Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte–Duclos disease. Nat Genet 29: 396–403.

    CAS  PubMed  Google Scholar 

  • Butler MG, Dasouki MJ, Zhou XP, Talebizadeh Z, Brown M, Takahashi TN et al. (2005). Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 42: 318–321.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chalhoub N, Kozma SC, Baker SJ . (2006). S6k1 is not required for Pten-deficient neuronal hypertrophy. Brain Res 1100: 32–41.

    CAS  PubMed  Google Scholar 

  • Crackower MA, Oudit GY, Kozieradzki I, Sarao R, Sun H, Sasaki T et al. (2002). Regulation of myocardial contractility and cell size by distinct PI3K–PTEN signaling pathways. Cell 110: 737–749.

    CAS  PubMed  Google Scholar 

  • DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI . (2003). Pathological and molecular aspects of prostate cancer. Lancet 361: 955–964.

    CAS  PubMed  Google Scholar 

  • Deocampo ND, Huang H, Tindall DJ . (2003). The role of PTEN in the progression and survival of prostate cancer. Minerva Endocrinol 28: 145–153.

    CAS  PubMed  Google Scholar 

  • Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP . (1999). Impaired Fas response and autoimmunity in Pten+/− mice. Science 285: 2122–2125.

    CAS  PubMed  Google Scholar 

  • Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP . (1998). Pten is essential for embryonic development and tumour suppression. Nat Genet 19: 348–355.

    CAS  PubMed  Google Scholar 

  • Ford-Hutchinson AF, Ali Z, Lines SE, Hallgrimsson B, Boyd SK, Jirik FR . (2007). Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth plate abnormalities and skeletal overgrowth. J Bone Miner Res 22: 1245–1259.

    CAS  PubMed  Google Scholar 

  • Fraser MM, Zhu X, Kwon CH, Uhlmann EJ, Gutmann DH, Baker SJ . (2004). Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo. Cancer Res 64: 7773–7779.

    CAS  PubMed  Google Scholar 

  • Groszer M, Erickson R, Scripture-Adams DD, Dougherty JD, Le Belle J, Zack JA et al. (2006). PTEN negatively regulates neural stem cell self-renewal by modulating G0–G1 cell cycle entry. Proc Natl Acad Sci USA 103: 111–116.

    CAS  PubMed  Google Scholar 

  • Groszer M, Erickson R, Scripture-Adams DD, Lesche R, Trumpp A, Zack JA et al. (2001). Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294: 2186–2189.

    CAS  PubMed  Google Scholar 

  • Gu G, Dubauskaite J, Melton DA . (2002). Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129: 2447–2457.

    CAS  PubMed  Google Scholar 

  • Hagenbeek TJ, Naspetti M, Malergue F, Garcon F, Nunes JA, Cleutjens KB et al. (2004). The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and pre-TCR-mediated signaling. J Exp Med 200: 883–894.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hagenbeek TJ, Spits H . (2008). T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus. Leukemia 22: 608–619.

    CAS  PubMed  Google Scholar 

  • Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J et al. (2005). The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev 19: 2054–2065.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Herman GE, Henninger N, Ratliff-Schaub K, Pastore M, Fitzgerald S, McBride KL . (2007). Genetic testing in autism: how much is enough? Genet Med 9: 268–274.

    PubMed  Google Scholar 

  • Hernando E, Charytonowicz E, Dudas ME, Menendez S, Matushansky I, Mills J et al. (2007). The AKT–mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med 13: 748–753.

    CAS  PubMed  Google Scholar 

  • He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA et al. (2007). PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 39: 189–198.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J et al. (2004). Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 113: 1774–1783.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue-Narita T, Hamada K, Sasaki T, Hatakeyama S, Fujita S, Kawahara K et al. (2008). Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis. Cancer Res 68: 5760–5768.

    CAS  PubMed  Google Scholar 

  • Kimura T, Suzuki A, Fujita Y, Yomogida K, Lomeli H, Asada N et al. (2003). Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production. Development 130: 1691–1700.

    CAS  PubMed  Google Scholar 

  • Kishimoto H, Ohteki T, Yajima N, Kawahara K, Natsui M, Kawarasaki S et al. (2007). The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells. Blood 109: 3316–3324.

    CAS  PubMed  Google Scholar 

  • Knobbe CB, Merlo A, Reifenberger G . (2002). Pten signaling in gliomas. Neuro Oncol 4: 196–211.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M . (2006). Expanding role of AMPK in endocrinology. Trends Endocrinol Metab 17: 205–215.

    CAS  PubMed  Google Scholar 

  • Kurlawalla-Martinez C, Stiles B, Wang Y, Devaskar SU, Kahn BB, Wu H . (2005). Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Mol Cell Biol 25: 2498–2510.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuroda S, Nishio M, Sasaki S, Horie Y, Kawahara K, Sasaki M et al. (2008). Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages. Eur J Immunol 38: 1–10.

    Google Scholar 

  • Kwon CH, Luikart BW, Powell CM, Zhou J, Matheny SA, Zhang W et al. (2006). Pten regulates neuronal arborization and social interaction in mice. Neuron 50: 377–388.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon CH, Zhu X, Zhang J, Baker SJ . (2003). mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo. Proc Natl Acad Sci USA 100: 12923–12928.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ et al. (2001). Pten regulates neuronal soma size: a mouse model of Lhermitte–Duclos disease. Nat Genet 29: 404–411.

    CAS  PubMed  Google Scholar 

  • Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N et al. (2002). Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129: 4159–4170.

    CAS  PubMed  Google Scholar 

  • Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI et al. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947.

    CAS  PubMed  Google Scholar 

  • Li Y, Podsypanina K, Liu X, Crane A, Tan LK, Parsons R et al. (2001). Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice. BMC Mol Biol 2: 2.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Babaian DC, Liebert M, Steck PA, Kagan J . (2000). Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens. Mol Carcinog 29: 143–150.

    CAS  PubMed  Google Scholar 

  • Liu X, Bruxvoort KJ, Zylstra CR, Liu J, Cichowski R, Faugere MC et al. (2007). Lifelong accumulation of bone in mice lacking Pten in osteoblasts. Proc Natl Acad Sci USA 104: 2259–2264.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lomeli H, Ramos-Mejia V, Gertsenstein M, Lobe CG, Nagy A . (2000). Targeted insertion of Cre recombinase into the TNAP gene: excision in primordial germ cells. Genesis 26: 116–117.

    CAS  PubMed  Google Scholar 

  • Lu TL, Chang JL, Liang CC, You LR, Chen CM . (2007). Tumor spectrum, tumor latency and tumor incidence of the pten-deficient mice. PLoS ONE 2: e1237.

    PubMed  PubMed Central  Google Scholar 

  • Ma X, Ziel-van der Made AC, Autar B, van der Korput HA, Vermeij M, van Duijn P et al. (2005). Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res 65: 5730–5739.

    CAS  PubMed  Google Scholar 

  • Maddison LA, Nahm H, DeMayo F, Greenberg NM . (2000). Prostate specific expression of Cre recombinase in transgenic mice. Genesis 26: 154–156.

    CAS  PubMed  Google Scholar 

  • Maehama T, Dixon JE . (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273: 13375–13378.

    CAS  PubMed  Google Scholar 

  • Marandola P, Bonghi A, Jallous H, Bombardelli E, Morazzoni P, Gerardini M et al. (2004). Molecular biology and the staging of prostate cancer. Ann NY Acad Sci 1028: 294–312.

    CAS  PubMed  Google Scholar 

  • Marino S, Krimpenfort P, Leung C, van der Korput HA, Trapman J, Camenisch I et al. (2002). PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development 129: 3513–3522.

    CAS  PubMed  Google Scholar 

  • Marsit CJ, Zheng S, Aldape K, Hinds PW, Nelson HH, Wiencke JK et al. (2005). PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol 36: 768–776.

    CAS  PubMed  Google Scholar 

  • Nguyen KT, Tajmir P, Lin CH, Liadis N, Zhu XD, Eweida M et al. (2006). Essential role of Pten in body size determination and pancreatic beta-cell homeostasis in vivo. Mol Cell Biol 26: 4511–4518.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R et al. (2007). Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cel Biol 9: 36–44.

    CAS  Google Scholar 

  • Ogawa S, Kwon CH, Zhou J, Koovakkattu D, Parada LF, Sinton CM . (2007). A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. Brain Res 1168: 112–123.

    CAS  PubMed  Google Scholar 

  • Oudit GY, Kassiri Z, Zhou J, Liu QC, Liu PP, Backx PH et al. (2008). Loss of PTEN attenuates the development of pathological hypertrophy and heart failure in response to biomechanical stress. Cardiovasc Res 78: 505–514.

    CAS  PubMed  Google Scholar 

  • Ovchinnikov DA, Deng JM, Ogunrinu G, Behringer RR . (2000). Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice. Genesis 26: 145–146.

    CAS  PubMed  Google Scholar 

  • Pasqualucci L, Bhagat G, Jankovic M, Compagno M, Smith P, Muramatsu M et al. (2008). AID is required for germinal center-derived lymphomagenesis. Nat Genet 40: 108–112.

    CAS  PubMed  Google Scholar 

  • Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H et al. (2006). Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Invest 116: 1886–1901.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM et al. (1999). Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci USA 96: 1563–1568.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Postic C, Magnuson MA . (2000). DNA excision in liver by an albumin–Cre transgene occurs progressively with age. Genesis 26: 149–150.

    CAS  PubMed  Google Scholar 

  • Postic C, Shiota M, Magnuson MA . (2001). Cell-specific roles of glucokinase in glucose homeostasis. Recent Prog Horm Res 56: 195–217.

    CAS  PubMed  Google Scholar 

  • Ratnacaram CK, Teletin M, Jiang M, Meng X, Chambon P, Metzger D . (2008). Temporally controlled ablation of PTEN in adult mouse prostate epithelium generates a model of invasive prostatic adenocarcinoma. Proc Natl Acad Sci USA 105: 2521–2526.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y et al. (2008). Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 319: 611–613.

    CAS  PubMed  Google Scholar 

  • Saal LH, Gruvberger-Saal SK, Persson C, Lovgren K, Jumppanen M, Staaf J et al. (2008). Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 40: 102–107.

    CAS  PubMed  Google Scholar 

  • Saam JR, Gordon JI . (1999). Inducible gene knockouts in the small intestinal and colonic epithelium. J Biol Chem 274: 38071–38082.

    CAS  PubMed  Google Scholar 

  • Shao J, Washington MK, Saxena R, Sheng H . (2007). Heterozygous disruption of the PTEN promotes intestinal neoplasia in APC−/+ mouse: roles of osteopontin. Carcinogenesis 28: 2476–2483.

    CAS  PubMed  Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al. (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98: 10869–10874.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T et al. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95: 29–39.

    CAS  PubMed  Google Scholar 

  • Stambolic V, Tsao MS, Macpherson D, Suzuki A, Chapman WB, Mak TW . (2000). High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/− mice. Cancer Res 60: 3605–3611.

    CAS  PubMed  Google Scholar 

  • Stanger BZ, Stiles B, Lauwers GY, Bardeesy N, Mendoza M, Wang Y et al. (2005). Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8: 185–195.

    CAS  PubMed  Google Scholar 

  • Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH et al. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15: 356–362.

    CAS  PubMed  Google Scholar 

  • Stiles B, Wang Y, Stahl A, Bassilian S, Lee WP, Kim YJ et al. (2004). Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity (corrected). Proc Natl Acad Sci USA 101: 2082–2087.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stiles BL, Kuralwalla-Martinez C, Guo W, Gregorian C, Wang Y, Tian J et al. (2006). Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes. Mol Cell Biol 26: 2772–2781.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Subramanian KK, Jia Y, Zhu D, Simms BT, Jo H, Hattori H et al. (2007). Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions. Blood 109: 4028–4037.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I et al. (1998). High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 8: 1169–1178.

    CAS  PubMed  Google Scholar 

  • Suzuki A, Hamada K, Sasaki T, Mak TW, Nakano T . (2007). Role of PTEN/PI3K pathway in endothelial cells. Biochem Soc Trans 35: 172–176.

    CAS  PubMed  Google Scholar 

  • Suzuki A, Itami S, Ohishi M, Hamada K, Inoue T, Komazawa N et al. (2003a). Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation. Cancer Res 63: 674–681.

    CAS  PubMed  Google Scholar 

  • Suzuki A, Kaisho T, Ohishi M, Tsukio-Yamaguchi M, Tsubata T, Koni PA et al. (2003b). Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. J Exp Med 197: 657–667.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki A, Sasaki T, Mak TW, Nakano T . (2004). Functional analysis of the tumour suppressor gene PTEN in murine B cells and keratinocytes. Biochem Soc Trans 32: 362–365.

    CAS  PubMed  Google Scholar 

  • Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y et al. (2001). T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14: 523–534.

    CAS  PubMed  Google Scholar 

  • Tang JM, He QY, Guo RX, Chang XJ . (2006). Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer 51: 181–191.

    PubMed  Google Scholar 

  • Taniyama K, Goodison S, Ito R, Bookstein R, Miyoshi N, Tahara E et al. (2001). PTEN expression is maintained in sporadic colorectal tumours. J Pathol 194: 341–348.

    CAS  PubMed  Google Scholar 

  • Teng Y, Sun AN, Pan XC, Yang G, Yang LL, Wang MR et al. (2006). Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse. Cancer Res 66: 6972–6981.

    CAS  PubMed  Google Scholar 

  • Trotman LC, Niki M, Dotan ZA, Koutcher JA, Di Cristofano A, Xiao A et al. (2003). Pten dose dictates cancer progression in the prostate. PLoS Biol 1: E59.

    PubMed  PubMed Central  Google Scholar 

  • Tsuruta H, Kishimoto H, Sasaki T, Horie Y, Natsui M, Shibata Y et al. (2006). Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients. Cancer Res 66: 8389–8396.

    CAS  PubMed  Google Scholar 

  • van Nederveen FH, Perren A, Dannenberg H, Petri BJ, Dinjens WN, Komminoth P et al. (2006). PTEN gene loss, but not mutation, in benign and malignant phaeochromocytomas. J Pathol 209: 274–280.

    CAS  PubMed  Google Scholar 

  • Wagner KU, McAllister K, Ward T, Davis B, Wiseman R, Hennighausen L . (2001). Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Res 10: 545–553.

    CAS  PubMed  Google Scholar 

  • Walker GJ, Hayward NK . (2002). Pathways to melanoma development: lessons from the mouse. J Invest Dermatol 119: 783–792.

    CAS  PubMed  Google Scholar 

  • Wang DS, Rieger-Christ K, Latini JM, Moinzadeh A, Stoffel J, Pezza JA et al. (2000). Molecular analysis of PTEN and MXI1 in primary bladder carcinoma. Int J Cancer 88: 620–625.

    CAS  PubMed  Google Scholar 

  • Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J et al. (2003). Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4: 209–221.

    CAS  PubMed  Google Scholar 

  • Wei Q, Clarke L, Scheidenhelm DK, Qian B, Tong A, Sabha N et al. (2006). High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Cancer Res 66: 7429–7437.

    CAS  PubMed  Google Scholar 

  • Wiestler OD, Padberg GW, Steck PA . (2000). Cowden Disease and Dysplastic Gangliocytoma of the Cerebellum/Lhermitte-Duclos Disease. In: Kleihues O, Cavenee WK (eds). WHO Classification of Tumours—Pathology and Genetics, Tumours of the Nervous System. IARC Press.

    Google Scholar 

  • Wijesekara N, Konrad D, Eweida M, Jefferies C, Liadis N, Giacca A et al. (2005). Muscle-specific Pten deletion protects against insulin resistance and diabetes. Mol Cell Biol 25: 1135–1145.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Wu J, Huang J, Powell WC, Zhang J, Matusik RJ et al. (2001). Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech Dev 101: 61–69.

    CAS  PubMed  Google Scholar 

  • Xue L, Nolla H, Suzuki A, Mak TW, Winoto A . (2008). Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice. Proc Natl Acad Sci USA 105: 2022–2027.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M et al. (2007). Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice. J Clin Invest 117: 2929–2940.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L, Mao C, Teng Y, Li W, Zhang J, Cheng X et al. (2005). Targeted disruption of Smad4 in mouse epidermis results in failure of hair follicle cycling and formation of skin tumors. Cancer Res 65: 8671–8678.

    CAS  PubMed  Google Scholar 

  • Yeager N, Klein-Szanto A, Kimura S, Di Cristofano A . (2007). Pten loss in the mouse thyroid causes goiter and follicular adenomas: insights into thyroid function and Cowden disease pathogenesis. Cancer Res 67: 959–966.

    CAS  PubMed  Google Scholar 

  • Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H et al. (2006). Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441: 475–482.

    CAS  PubMed  Google Scholar 

  • Yoo LI, Liu DW, Le Vu S, Bronson RT, Wu H, Yuan J . (2006). Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner. Cancer Res 66: 1929–1939.

    CAS  PubMed  Google Scholar 

  • You MJ, Castrillon DH, Bastian BC, O’Hagan RC, Bosenberg MW, Parsons R et al. (2002). Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice. Proc Natl Acad Sci USA 99: 1455–1460.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yue Q, Groszer M, Gil JS, Berk AJ, Messing A, Wu H et al. (2005). PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization. Development 132: 3281–3291.

    CAS  PubMed  Google Scholar 

  • Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT et al. (2006). PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441: 518–522.

    CAS  PubMed  Google Scholar 

  • Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC et al. (2002). Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem 277: 44005–44012.

    CAS  PubMed  Google Scholar 

  • Zhu D, Hattori H, Jo H, Jia Y, Subramanian KK, Loison F et al. (2006). Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates neutrophil spontaneous death. Proc Natl Acad Sci USA 103: 14836–14841.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Mary Saunders for editing. CBK is supported by the Alexander-von-Humboldt Foundation. VL is supported by a Doctoral Research Award from the Canadian Institutes of Health Research.

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  1. C B Knobbe and V Lapin: These authors contributed equally to this work.

Authors and Affiliations

  1. Campbell Family Institute for Breast Cancer Research, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, Canada

    C B Knobbe, V Lapin & T W Mak

  2. Department of Medical Biophysics, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, Canada

    V Lapin & T W Mak

  3. Division of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    A Suzuki

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  1. C B Knobbe
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Correspondence to T W Mak.

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Knobbe, C., Lapin, V., Suzuki, A. et al. The roles of PTEN in development, physiology and tumorigenesis in mouse models: a tissue-by-tissue survey. Oncogene 27, 5398–5415 (2008). https://doi.org/10.1038/onc.2008.238

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