Inhibition of mTOR Reduces Anal Carcinogenesis in Transgenic Mouse Model

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Sun, Zhi Jun ^a,b   Zhang, Lu ^a,b   Zhang, Wei ^a   Hall, Bradford ^b   Bian, Yansong ^c   Kulkarni, Ashok B ^b  

^a Wuhan University   (China)

^b NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN S6; RAPAMYCIN; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANUS CARCINOMA; ARTICLE; CANCER INHIBITION; CANCER MODEL; CANCER SUSCEPTIBILITY; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; GENE DELETION; HISTOPATHOLOGY; KNOCKOUT MOUSE; MALE; MOUSE; NONHUMAN; PRECANCER; PROTEIN PHOSPHORYLATION; PTEN GENE; SQUAMOUS CELL CARCINOMA; TGFBR1 GENE; TREATMENT DURATION; TUMOR VOLUME;

ANIMALS; ANTI-BACTERIAL AGENTS; ANUS NEOPLASMS; BLOTTING, WESTERN; FEMALE; IMMUNOHISTOCHEMISTRY; IN SITU NICK-END LABELING; MALE; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PTEN PHOSPHOHYDROLASE; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84885075825     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0074888     Document Type: Article

References (33)

1. Johnson LG, Madeleine MM, Newcomer LM, Schwartz SM, Daling JR, (2004) Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 101: 281-288.
2. Cress RD, Holly EA, (2003) Incidence of anal cancer in California: increased incidence among men in San Francisco, 1973-1999. Prev Med 36: 555-560.
3. Thomas MK, Pitot HC, Liem A, Lambert PF, (2011) Dominant role of HPV16 E7 in anal carcinogenesis. Virology 421: 114-118.
4. Szmulowicz UM, Wu JS, (2012) Squamous cell carcinoma of the anal canal: a review of the aetiology, presentation, staging, prognosis and methods available for treatment. Sex Health 9: 593-609.
5. Hoot KE, Lighthall J, Han G, Lu SL, Li A, et al. (2008) Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest 118: 2722-2732.
6. Stelzer MK, Pitot HC, Liem A, Schweizer J, Mahoney C, et al. (2010) A mouse model for human anal cancer. Cancer Prev Res (Phila) 3: 1534-1541.
7. Patel H, Polanco-Echeverry G, Segditsas S, Volikos E, McCart A, et al. (2007) Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma. Int J Cancer 121: 2668-2673.
8. Mitsuishi T, Iwabu Y, Tokunaga K, Sata T, Kaneko T, et al. (2010) Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors. BMC Cancer 10: 118.
9. Di Cristofano A, Pandolfi PP, (2000) The multiple roles of PTEN in tumor suppression. Cell 100: 387-390.
10. Massague J, (2008) TGFbeta in Cancer. Cell 134: 215-230.
11. Shi Y, Massague J, (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113: 685-700.
12. Bian Y, Terse A, Du J, Hall B, Molinolo A, et al. (2009) Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3K/Akt pathway. Cancer Res 69: 5918-5926.
13. Bian Y, Hall B, Sun ZJ, Molinolo A, Chen W, et al. (2012) Loss of TGF-beta signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. Oncogene 31: 3322-3332.
14. Stelzer MK, Pitot HC, Liem A, Lee D, Kennedy GD, et al. (2010) Rapamycin inhibits anal carcinogenesis in two preclinical animal models. Cancer Prev Res (Phila) 3: 1542-1551.
15. Honjo Y, Bian Y, Kawakami K, Molinolo A, Longenecker G, et al. (2007) TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma. Cell Cycle 6: 1360-1366.
16. Sun ZJ, Zhang L, Hall B, Bian Y, Gutkind JS, et al. (2012) Chemopreventive and chemotherapeutic actions of mTOR inhibitor in genetically defined head and neck squamous cell carcinoma mouse model. Clin Cancer Res 18: 5304-5313.
17. Zhang L, Sun ZJ, Bian Y, Kulkarni AB, (2013) MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett 331: 230-238.
18. Guasch G, Schober M, Pasolli HA, Conn EB, Polak L, et al. (2007) Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12: 313-327.
19. Liang C, Marsit CJ, McClean MD, Nelson HH, Christensen BC, et al. (2012) Biomarkers of HPV in Head and Neck Squamous Cell Carcinoma. Cancer Res 72: 5004-5013.
20. Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, Sauk JJ, et al. (2005) Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res 65: 9953-9961.
21. Shin KH, Park YJ, Park JG, (2001) PTEN gene mutations in colorectal cancers displaying microsatellite instability. Cancer Lett 174: 189-194.
22. Mao C, Zhou J, Yang Z, Huang Y, Wu X, et al. (2012) KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer. PLoS One 7: e36653.
23. Snietura M, Jaworska M, Mlynarczyk-Liszka J, Goraj-Zajac A, Piglowski W, et al. (2012) PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck. PLoS One 7: e33396.
24. Diaz-Chavez J, Hernandez-Pando R, Lambert PF, Gariglio P, (2008) Down-regulation of transforming growth factor-beta type II receptor (TGF-betaRII) protein and mRNA expression in cervical cancer. Mol Cancer 7: 3.
25. Wakefield LM, Roberts AB, (2002) TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev 12: 22-29.
26. Yoshinaga K, Obata H, Jurukovski V, Mazzieri R, Chen Y, et al. (2008) Perturbation of transforming growth factor (TGF)-beta1 association with latent TGF-beta binding protein yields inflammation and tumors. Proc Natl Acad Sci U S A 105: 18758-18763.
27. Hahm KB, Im YH, Parks TW, Park SH, Markowitz S, et al. (2001) Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease. Gut 49: 190-198.
28. Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, et al. (2012) TGF-beta signalling in colon carcinogenesis. Cancer Lett 314: 1-7.
29. Sabatini DM, (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6: 729-734.
30. Weichhart T, Saemann MD, (2009) The multiple facets of mTOR in immunity. Trends Immunol 30: 218-226.
31. Wullschleger S, Loewith R, Hall MN, (2006) TOR signaling in growth and metabolism. Cell 124: 471-484.
32. Haxhinasto S, Mathis D, Benoist C, (2008) The AKT-mTOR axis regulates de novo differentiation of CD4 + Foxp3 + cells. J Exp Med 205: 565-574.
33. Lee JH, Lydon JP, Kim CH, (2012) Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability. Eur J Immunol 42: 2683-2696.