microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion

PLoS ONE

Volumn 7, Issue 6, 2012, Pages

  Dey, Nirmalya ^a   Das, Falguni ^a   Ghosh Choudhury, Nandini ^a,b   Mandal, Chandi Charan ^a   Parekh, Dipen J ^a   Block, Karen ^a,b   Kasinath, Balakuntalam S ^a,b   Abboud, Hanna E ^a,b   Choudhury, Goutam Ghosh ^a,b  

^a Mays Cancer Center at UT Health San Antonio   (United States)

^b SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MICRORNA 21; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; TUBERIN;

3' UNTRANSLATED REGION; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER CELL; CELL INVASION; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; HUMAN; HUMAN CELL; HUMAN TISSUE; KIDNEY CANCER; KIDNEY TUBULE CELL; MIGRATION INHIBITION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TRANSCRIPTION INITIATION; TUMOR SUPPRESSOR GENE;

3' UNTRANSLATED REGIONS; CARCINOMA, RENAL CELL; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOBLOTTING; KIDNEY NEOPLASMS; MICRORNAS; MODELS, GENETIC; NEOPLASM INVASIVENESS; PHOSPHORYLATION; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 84861887145     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0037366     Document Type: Article

References (118)

1. Novick AC, (2007) Kidney cancer: past, present, and future. Urol Oncol 25: 188-195.
2. Rouviere O, Bouvier R, Negrier S, Badet L, Lyonnet D, (2006) Nonmetastatic renal-cell carcinoma: is it really possible to define rational guidelines for post-treatment follow-up? Nat Clin Pract Oncol 3: 200-213.
3. Milowsky MI, Nanus DM, (2003) Chemotherapeutic strategies for renal cell carcinoma. Urol Clin North Am 30: 601-609, x.
4. Kaelin WG Jr, (2002) Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2: 673-682.
5. Kaelin WG Jr, (2009) Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 115: 2262-2272.
6. Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, et al. (2008) VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 10: 361-369.
7. Kaelin WG Jr, (2008) The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer 8: 865-873.
8. Bartel DP, (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281-297.
9. Bartel DP, (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215-233.
10. Couzin J, (2008) MicroRNAs make big impression in disease after disease. Science 319: 1782-1784.
11. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, et al. (2005) A microRNA polycistron as a potential human oncogene. Nature 435: 828-833.
12. Fabian MR, Sonenberg N, Filipowicz W, (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79: 351-379.
13. Yang JS, Lai EC, (2011) Alternative miRNA Biogenesis Pathways and the Interpretation of Core miRNA Pathway Mutants. Mol Cell 43: 892-903.
14. Juan D, Alexe G, Antes T, Liu H, Madabhushi A, et al. (2010) Identification of a microRNA panel for clear-cell kidney cancer. Urology 75: 835-841.
15. Petillo D, Kort EJ, Anema J, Furge KA, Yang XJ, et al. (2009) MicroRNA profiling of human kidney cancer subtypes. Int J Oncol 35: 109-114.
16. Nakada C, Matsuura K, Tsukamoto Y, Tanigawa M, Yoshimoto T, et al. (2008) Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol 216: 418-427.
17. Huang Y, Dai Y, Yang J, Chen T, Yin Y, et al. (2009) Microarray analysis of microRNA expression in renal clear cell carcinoma. Eur J Surg Oncol 35: 1119-1123.
18. Volinia S, Galasso M, Costinean S, Tagliavini L, Gamberoni G, et al. (2010) Reprogramming of miRNA networks in cancer and leukemia. Genome Res 20: 589-599.
19. Powers MP, Alvarez K, Kim HJ, Monzon FA, (2011) Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping. Diagn Mol Pathol 20: 63-70.
20. Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A, (2011) Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. Mol Cell 39: 373-384.
21. Zhou R, Hu G, Gong AY, Chen XM, (2010) Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res 38: 3222-3232.
22. Oya M, Takayanagi A, Horiguchi A, Mizuno R, Ohtsubo M, et al. (2003) Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma. Carcinogenesis 24: 377-384.
23. Oya M, Ohtsubo M, Takayanagi A, Tachibana M, Shimizu N, et al. (2001) Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells. Oncogene 20: 3888-3896.
24. Madrid LV, Mayo MW, Reuther JY, Baldwin AS Jr, (2001) Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem 276: 18934-18940.
25. Dey N, Das F, Mariappan MM, Mandal CC, Ghosh-Choudhury N, et al. (2011) MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem 286: 25586-25603.
26. Ebert MS, Neilson JR, Sharp PA, (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4: 721-726.
27. Cully M, You H, Levine AJ, Mak TW, (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6: 184-192.
28. Salmena L, Carracedo A, Pandolfi PP, (2008) Tenets of PTEN tumor suppression. Cell 133: 403-414.
29. Abou Youssif T, Fahmy MA, Koumakpayi IH, Ayala F, Al Marzooqi S, et al. (2010) The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases. Cancer 117: 290-300.
30. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, et al. (2006) Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130: 2113-2129.
31. 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.
32. Cantley LC, Neel BG, (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 96: 4240-4245.
33. van Weering DH, de Rooij J, Marte B, Downward J, Bos JL, et al. (1998) Protein kinase B activation and lamellipodium formation are independent phosphoinositide 3-kinase-mediated events differentially regulated by endogenous Ras. Mol Cell Biol 18: 1802-1811.
34. Manning BD, Logsdon MN, Lipovsky AI, Abbott D, Kwiatkowski DJ, et al. (2005) Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev 19: 1773-1778.
35. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC, (2002) Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell 10: 151-162.
36. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J, (2003) Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 13: 1259-1268.
37. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, et al. (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133: 647-658.
38. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435: 834-838.
39. Si ML, Zhu S, Wu H, Lu Z, Wu F, et al. (2007) miR-21-mediated tumor growth. Oncogene 26: 2799-2803.
40. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, et al. (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65: 7065-7070.
41. Chan JA, Krichevsky AM, Kosik KS, (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65: 6029-6033.
42. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, et al. (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299: 425-436.
43. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, et al. (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9: 189-198.
44. Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, et al. (2007) MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 121: 1156-1161.
45. Navarro A, Gaya A, Martinez A, Urbano-Ispizua A, Pons A, et al. (2008) MicroRNA expression profiling in classic Hodgkin lymphoma. Blood 111: 2825-2832.
46. Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, et al. (2010) Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell 18: 282-293.
47. Medina PP, Nolde M, Slack FJ, (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467: 86-90.
48. Papagiannakopoulos T, Shapiro A, Kosik KS, (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68: 8164-8172.
49. Krichevsky AM, Gabriely G, (2009) miR-21: a small multi-faceted RNA. J Cell Mol Med 13: 39-53.
50. Saal S, Harvey SJ, (2009) MicroRNAs and the kidney: coming of age. Curr Opin Nephrol Hypertens 18: 317-323.
51. Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, et al. (2010) Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci U S A 107: 14339-14344.
52. Denby L, Ramdas V, McBride MW, Wang J, Robinson H, et al. (2011) miR-21 and miR-214 are consistently modulated during renal injury in rodent models. Am J Pathol 179: 661-672.
53. Zarjou A, Yang S, Abraham E, Agarwal A, Liu G, (2011) Identification of a microRNA signature in renal fibrosis: role of miR-21. Am J Physiol Renal Physiol 301: F793-801.
54. Kato M, Arce L, Natarajan R, (2009) MicroRNAs and their role in progressive kidney diseases. Clin J Am Soc Nephrol 4: 1255-1266.
55. Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB, Gleadle JM, (2010) The VHL-dependent regulation of microRNAs in renal cancer. BMC Med 8: 64.
56. Yi Z, Fu Y, Zhao S, Zhang X, Ma C, (2011) Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol 136: 855-862.
57. Banks RE, Tirukonda P, Taylor C, Hornigold N, Astuti D, et al. (2006) Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res 66: 2000-2011.
58. Nickerson ML, Jaeger E, Shi Y, Durocher JA, Mahurkar S, et al. (2008) Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin Cancer Res 14: 4726-4734.
59. Smits KM, Schouten LJ, van Dijk BA, Hulsbergen-van de Kaa CA, Wouters KA, et al. (2008) Genetic and epigenetic alterations in the von hippel-lindau gene: the influence on renal cancer prognosis. Clin Cancer Res 14: 782-787.
60. Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, et al. (2010) The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res 16: 3628-3638.
61. Weber K, Doucet M, Kominsky S, (2007) Renal cell carcinoma bone metastasis-elucidating the molecular targets. Cancer Metastasis Rev 26: 691-704.
62. Davis BN, Hilyard AC, Lagna G, Hata A, (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454: 56-61.
63. Vadas O, Burke JE, Zhang X, Berndt A, Williams RL, (2011) Structural basis for activation and inhibition of class I phosphoinositide 3-kinases. Sci Signal 4.
64. Castaneda CA, Cortes-Funes H, Gomez HL, Ciruelos EM, (2010) The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. Cancer Metastasis Rev 29: 751-759.
65. Hollander MC, Blumenthal GM, Dennis PA, (2011) PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer 11: 289-301.
66. Cairns P, Evron E, Okami K, Halachmi N, Esteller M, et al. (1998) Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene 16: 3215-3218.
67. Shin Lee J, Seok Kim H, Bok Kim Y, Cheol Lee M, Soo Park C, (2003) Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth. J Surg Oncol 84: 166-172.
68. Ghosh-Choudhury T, Mandal CC, Woodruff K, St Clair P, Fernandes G, et al. (2009) Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Breast Cancer Res Treat 118: 213-228.
69. Wang X, Jiang X, (2008) Post-translational regulation of PTEN. Oncogene 27: 5454-5463.
70. Hanahan D, Weinberg RA, (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674.
71. Bennett KL, Campbell R, Ganapathi S, Zhou M, Rini B, et al. (2011) Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma. Genes Chromosomes Cancer 50: 654-661.
72. He L, (2010) Posttranscriptional regulation of PTEN dosage by noncoding RNAs. Sci Signal 3: pe39.
73. Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, et al. (2010) Identification of the miR-106 b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal 3: ra29.
74. Pasquinelli AE, (2010) Molecular biology. Paring miRNAs through pairing. Science 328: 1494-1495.
75. Poon JS, Eves R, Mak AS, (2010) Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway. Cell Cycle 9: 4450-4454.
76. Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, et al. (1998) Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280: 1614-1617.
77. Mahimainathan L, Choudhury GG, (2004) Inactivation of platelet-derived growth factor receptor by the tumor suppressor PTEN provides a novel mechanism of action of the phosphatase. J Biol Chem 279: 15258-15268.
78. Dey N, Crosswell HE, De P, Parsons R, Peng Q, et al. (2008) The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration. Cancer Res 68: 1862-1871.
79. Gu J, Tamura M, Yamada KM, (1998) Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J Cell Biol 143: 1375-1383.
80. Davidson L, Maccario H, Perera NM, Yang X, Spinelli L,et al. Suppression of cellular proliferation and invasion by the concerted lipid and protein phosphatase activities of PTEN. Oncogene 29: 687-697.
81. Stocker H, Andjelkovic M, Oldham S, Laffargue M, Wymann MP, et al. (2002) Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295: 2088-2091.
82. Perez-Tenorio G, Alkhori L, Olsson B, Waltersson MA, Nordenskjold B, et al. (2007) PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 13: 3577-3584.
83. Stiles B, Groszer M, Wang S, Jiao J, Wu H, (2004) PTENless means more. Dev Biol 273: 175-184.
84. Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, et al. (1996) Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85: 707-720.
85. Di Cristofano A, De Acetis M, Koff A, Cordon-Cardo C, Pandolfi PP, (2001) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat Genet 27: 222-224.
86. Dahinden C, Ingold B, Wild P, Boysen G, Luu VD, et al. (2010) Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer. Clin Cancer Res 16: 88-98.
87. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, et al. (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110: 177-189.
88. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, et al. (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10: 457-468.
89. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, et al. (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14: 1296-1302.
90. Wullschleger S, Loewith R, Hall MN, (2006) TOR signaling in growth and metabolism. Cell 124: 471-484.
91. Zoncu R, Efeyan A, Sabatini DM, (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12: 21-35.
92. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM, (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101.
93. Sonenberg N, Hinnebusch AG, (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136: 731-745.
94. Manning BD, Cantley LC, (2007) AKT/PKB signaling: navigating downstream. Cell 129: 1261-1274.
95. Ohne Y, Takahara T, Hatakeyama R, Matsuzaki T, Noda M, et al. (2008) Isolation of hyperactive mutants of mammalian target of rapamycin. J Biol Chem 283: 31861-31870.
96. Gan X, Wang J, Su B, Wu D, (2011) Evidence for direct activation of mTORC2 kinase activity by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 286: 10998-11002.
97. Zinzalla V, Stracka D, Oppliger W, Hall MN, (2011) Activation of mTORC2 by association with the ribosome. Cell 144: 757-768.
98. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, et al. (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6: 1122-1128.
99. Liu L, Chen L, Chung J, Huang S, (2008) Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins. Oncogene 27: 4998-5010.
100. Liu L, Li F, Cardelli JA, Martin KA, Blenis J, et al. (2006) Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 25: 7029-7040.
101. Luan FL, Ding R, Sharma VK, Chon WJ, Lagman M, et al. (2003) Rapamycin is an effective inhibitor of human renal cancer metastasis. Kidney Int 63: 917-926.
102. Zhou H, Huang S, (2010) mTOR signaling in cancer cell motility and tumor metastasis. Crit Rev Eukaryot Gene Expr 20: 1-16.
103. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, et al. (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22: 909-918.
104. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, et al. (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116: 4256-4265.
105. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, et al. (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372: 449-456.
106. Traynor K, (2009) New oral treatment for kidney cancer approved. Am J Health Syst Pharm 66: 788.
107. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, et al. (2004) The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166: 213-223.
108. Shah OJ, Wang Z, Hunter T, (2004) Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol 14: 1650-1656.
109. Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, et al. (2008) Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5: e8.
110. Block K, Gorin Y, Hoover P, Williams P, Chelmicki T, et al. (2007) NAD(P)H oxidases regulate HIF-2alpha protein expression. J Biol Chem 282: 8019-8026.
111. Mandal CC, Ghosh-Choudhury N, Yoneda T, Choudhury GG, (2011) Simvastatin prevents skeletal metastasis of breast cancer by an antagonistic interplay between p53 and CD44. J Biol Chem 286: 11314-11327.
112. Choudhury GG, Ghosh-Choudhury N, Abboud HE, (1998) Association and direct activation of signal transducer and activator of transcription1alpha by platelet-derived growth factor receptor. J Clin Invest 101: 2751-2760.
113. Das F, Ghosh-Choudhury N, Mahimainathan L, Venkatesan B, Feliers D, et al. (2008) Raptor-rictor axis in TGFbeta-induced protein synthesis. Cell Signal 20: 409-423.
114. Dey N, Ghosh-Choudhury N, Das F, Li X, Venkatesan B, et al. (2010) PRAS40 acts as a nodal regulator of high glucose-induced TORC1 activation in glomerular mesangial cell hypertrophy. J Cell Physiol 225: 27-41.
115. Venkatesan B, Ghosh-Choudhury N, Das F, Mahimainathan L, Kamat A, et al. (2008) Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. FASEB J 22: 3469-3482.
116. Ghosh-Choudhury N, Mandal CC, Ghosh Choudhury G, (2010) Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal 22: 749-758.
117. Mahimainathan L, Ghosh-Choudhury N, Venkatesan B, Das F, Mandal CC, et al. (2009) TSC2 deficiency increases PTEN via HIF1alpha. J Biol Chem 284: 27790-27798.
118. Mahimainathan L, Das F, Venkatesan B, Choudhury GG, (2006) Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN. Diabetes 55: 2115-2125.