PPP2R2C loss promotes castration-resistance and is associated with increased prostate cancer-specific mortality

Molecular Cancer Research

Volumn 11, Issue 6, 2013, Pages 568-578

  Bluemn, Eric G ^a,b   Spencer, Elysia Sophie ^a   Mecham, Brigham ^b,c   Gordon, Ryan R ^b   Coleman, Ilsa ^b   Lewinshtein, Daniel ^b,d   Mostaghel, Elahe ^a,b   Zhang, Xiaotun ^a   Annis, James ^a,d   Grandori, Carla ^a,b,d   Porter, Christopher ^d   Nelson, Peter S ^a,b  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b USA   (United States)

^c SAGE BIONETWORKS   (United States)

^d VIRGINIA MASON MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DASATINIB; ENZALUTAMIDE; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 2A; PP2R2C PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CANCER CELL; CANCER GROWTH; CANCER MORTALITY; CASTRATION RESISTANT PROSTATE CANCER; CELL PROLIFERATION; CELL STRAIN LNCAP; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVE SITE; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MALE; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; RECURRENT CANCER; RNA INTERFERENCE;

ANDROGENS; CELL LINE, TUMOR; CELL PROLIFERATION; DOWN-REGULATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKDOWN TECHNIQUES; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MALE; MULTIVARIATE ANALYSIS; NEOPLASM METASTASIS; PHOSPHATIDYLINOSITOL 3-KINASES; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; PROTEIN PHOSPHATASE 2; RECEPTORS, ANDROGEN; RECURRENCE; RNA INTERFERENCE; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; TREATMENT OUTCOME;

EID: 84879316438     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-12-0710     Document Type: Article

References (29)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
2. Pagliarulo V, Bracarda S, Eisenberger MA, Mottet N, Schroder FH, Sternberg CN, et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol 2012;61:11-25.
3. Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006;24:3089-94.
4. Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 2010;375:1437-46.
5. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005.
6. Bluemn EG, Nelson PS. The androgen/androgen receptor axis in prostate cancer. Curr Opin Oncol 2012;24:251-7.
7. Nelson PS. Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J Clin Oncol 2012;30:644-6.
8. Mulholland DJ, Tran LM, Li Y, Cai H, Morim A, Wang S, et al. Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell 2011;19:792-804.
9. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chan-darlapaty S, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 2011;19:575-86.
10. Eichhorn PJ, Creyghton MP, Bernards R. Protein phosphatase 2A regulatory subunits and cancer. Biochim Biophys Acta 2009;1795: 1-15.
11. Millward TA, Zolnierowicz S, Hemmings BA. Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 1999;24:186-91.
12. Sablina AA, Hahn WC. The role of PP2A A subunits in tumor suppression. Cell Adhes Migr 2007;1:140-1.
13. Sablina AA, Hector M, Colpaert N, Hahn WC. Identification of PP2A complexes and pathways involved in cell transformation. Cancer Res 2010;70:10474-84.
14. Arroyo JD, Hahn WC. Involvement of PP2A in viral and cellular transformation. Oncogene 2005;24:7746-55.
15. Singh AP, Bafna S, Chaudhary K, Venkatraman G, Smith L, Eudy JD, et al. Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells. Cancer Lett 2008; 259:28-38.
16. Mao X, Boyd LK, Yanez-Munoz RJ, Chaplin T, Xue L, Lin D, et al. Chromosome rearrangement associated inactivation of tumour suppressor genes in prostate cancer. Am J Cancer Res 2011;1:604-17.
17. Bhardwaj A, Singh S, Srivastava SK, Honkanen RE, Reed E, Singh AP. Modulation of protein phosphatase 2A activity alters androgen-inde-pendent growth of prostate cancer cells: therapeutic implications. Mol Cancer Ther 2011;10:720-31.
18. Holcomb IN, Young JM, Coleman IM, Salari K, Grove DI, Hsu L, et al. Comparative analyses of chromosome alterations in soft-tissue metastases within and across patients with castration-resistant prostate cancer. Cancer Res 2009;69:7793-802.
19. True L, Coleman I, Hawley S, Huang CY, Gifford D, Coleman R, et al. A molecular correlate to the Gleason grading system for prostate ade-nocarcinoma. Proc Natl Acad Sci U S A 2006;103:10991-6.
20. Page ST, Lin DW, Mostaghel EA, Marck BT, Wright JL, Wu J, et al. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial. J Clin Endocrinol Metab 2011;96:430-7.
21. Bartz SR, Zhang Z, Burchard J, Imakura M, Martin M, Palmieri A, et al. Small interfering RNA screens reveal enhanced cisplatin cytotoxicity in tumor cells having both BRCA network and TP53 disruptions. Mol Cell Biol 2006;26:9377-86.
22. Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE, Chang AN, et al. Functional genomics identifies therapeutic targets for MYC-driven cancer. Proc Natl Acad Sci U S A 2012;109: 9545-50.
23. Eichhorn PJ, Creyghton MP, Wilhelmsen K, van Dam H, Bernards R. A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC. PLoS Genet 2007;3:e218.
24. Kobayashi T, Inoue T, Shimizu Y, Terada N, Maeno A, Kajita Y, et al. Activation of Rac1 is closely related to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo. Mol Endocrinol 2010;24:722-34.
25. Mendiratta P, Mostaghel E, Guinney J, Tewari AK, Porrello A, Barry WT, et al. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol 2009;27:2022-9.
26. Drake JM, Graham NA, Stoyanova T, Sedghi A, Goldstein AS, Cai H, et al. Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. Proc Natl Acad Sci U S A 2012;109: 1643-8.
27. Strack S, Zaucha JA, Ebner FF, Colbran RJ, Wadzinski BE. Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits. J Comp Neurol 1998;392: 515-27.
28. Guo CY, Brautigan DL, Larner JM. ATM-dependent dissociation of B55 regulatory subunit from nuclear PP2A in response to ionizing radiation. J Biol Chem 2002;277:4839-44.
29. O'Shaughnessy RF, Welti JC, Sully K, Byrne C. Akt-dependent Pp2a activity is required for epidermal barrier formation during late embryonic development. Development 2009;136:3423-31.