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The E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate cancer

dc.contributor.authorValdez, Conrad Daviden_US
dc.contributor.authorKunju, Lakshmien_US
dc.contributor.authorDaignault, Stephanieen_US
dc.contributor.authorWojno, Kirk J.en_US
dc.contributor.authorDay, Mark L.en_US
dc.date.accessioned2013-11-01T19:01:12Z
dc.date.available2015-01-05T13:54:45Zen_US
dc.date.issued2013-12en_US
dc.identifier.citationValdez, Conrad David; Kunju, Lakshmi; Daignault, Stephanie; Wojno, Kirk J.; Day, Mark L. (2013). "The E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate cancer." The Prostate 73(16): 1776-1785.en_US
dc.identifier.issn0270-4137en_US
dc.identifier.issn1097-0045en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/100341
dc.description.abstractBACKGROUND Research on castration resistant prostate cancer (CRPC) has focused primarily on functional alterations of the androgen receptor (AR). However, little is known about the loss of AR gene expression itself and the possible contribution of AR negative cells to CRPC. METHODS Human and murine prostate cancer tissue microarrays (TMAs) were evaluated with antibodies specific for E2F1, DNA methyltransferase 1 or AR. The human prostate cancer TMA consisted of clinical samples ranging from normal tissue to samples of metastatic disease. The murine TMA was comprised of benign, localized or metastatic prostate cancer acquired from TRAMP mice treated with castration and/or 5′‐Aza‐2′‐deoxycytidine (5Aza). RESULTS Immunohistochemical analysis revealed increased nuclear DNMT1 staining in localized PCa ( P  < 0.0001) and metastatic PCa ( P  < 0.0001) compared to normal tissue. Examination of specific diagnoses revealed that Gleason seven tumors exhibited greater nuclear DNMT1 staining than Gleason six tumors ( P  < 0.05) and that metastatic tissue exhibited greater levels of nuclear DNMT1 than Gleason seven tumors ( P  < 0.01). Evaluation of the murine tissue cores revealed that 8.2% and 8.1% of benign tissue cores stained positive for E2F1 and DNMT1 respectively, while 97.0% were AR positive. Conversely, 81% and 100% of tumors were positive for E2F1and DNMT1 respectively. This was in stark contrast to only 18% of tumors positive for AR. Treatment of mice with 5Aza reduced DNMT1 staining by 30%, while AR increased by 27%. CONCLUSIONS These findings demonstrate that the E2F1/DNMT1 inhibitory axis of AR transcription is activated during the emergence of CRPC. Prostate 73:1776–1785, 2013 . © 2013 Wiley Periodicals, Inc.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherDNMT1en_US
dc.subject.otherTissue Microarrayen_US
dc.subject.otherImmunohistochemistryen_US
dc.subject.otherMethylationen_US
dc.subject.otherE2F1en_US
dc.subject.otherAndrogen Receptoren_US
dc.titleThe E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate canceren_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelInternal Medicine and Specialtiesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/100341/1/pros22715.pdf
dc.identifier.doi10.1002/pros.22715en_US
dc.identifier.sourceThe Prostateen_US
dc.identifier.citedreferenceSasaki M, Tanaka Y, Perinchery G, Dharia A, Kotcherguina I, Fujimoto S, Dahiya R. Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer. J Natl Cancer Inst 2002; 94 ( 5 ): 384 – 390.en_US
dc.identifier.citedreferencePatra SK, Patra A, Zhao H, Dahiya R. DNA methyltransferase and demethylase in human prostate cancer. Mol Carcinog 2002; 33 ( 3 ): 163 – 171.en_US
dc.identifier.citedreferenceTomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana‐Sundaram S, Wei JT, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM. Integrative molecular concept modeling of prostate cancer progression. Nat Genet 2007; 39 ( 1 ): 41 – 51.en_US
dc.identifier.citedreferenceKinney SR, Moser MT, Pascual M, Greally JM, Foster BA, Karpf AR. Opposing roles of Dnmt1 in early‐ and late‐stage murine prostate cancer. Mol Cell Biol 2010; 30 ( 17 ): 4159 – 4174.en_US
dc.identifier.citedreferenceYu YP, Paranjpe S, Nelson J, Finkelstein S, Ren B, Kokkinakis D, Michalopoulos G, Luo JH. High throughput screening of methylation status of genes in prostate cancer using an oligonucleotide methylation array. Carcinogenesis 2005; 26 ( 2 ): 471 – 479.en_US
dc.identifier.citedreferenceValdez CD, Davis JN, Odeh HM, Layfield TL, Cousineau CS, Berton TR, Johnson DG, Wojno KJ, Day ML. Repression of androgen receptor transcription through the E2F1/DNMT1 axis. PLoS ONE 2011; 6 ( 9 ): e25187.en_US
dc.identifier.citedreferenceGreenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ, Rosen JM. Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 1995; 92 ( 8 ): 3439 – 3443.en_US
dc.identifier.citedreferenceZorn CS, Wojno KJ, McCabe MT, Kuefer R, Gschwend JE, Day ML. 5‐Aza‐2′‐deoxycytidine delays androgen‐independent disease and improves survival in the transgenic adenocarcinoma of the mouse prostate mouse model of prostate cancer. Clin Cancer Res 2007; 13 ( 7 ): 2136 – 2143.en_US
dc.identifier.citedreferenceGingrich JR, Barrios RJ, Kattan MW, Nahm HS, Finegold MJ, Greenberg NM. Androgen‐independent prostate cancer progression in the TRAMP model. Cancer Res 1997; 57 ( 21 ): 4687 – 4691.en_US
dc.identifier.citedreferenceMutze K, Langer R, Schumacher F, Becker K, Ott K, Novotny A, Hapfelmeier A, Hofler H, Keller G. DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer. Eur J Cancer 2011; 47 ( 12 ): 1817 – 1825.en_US
dc.identifier.citedreferenceJarrard DF, Kinoshita H, Shi Y, Sandefur C, Hoff D, Meisner LF, Chang C, Herman JG, Isaacs WB, Nassif N. Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells. Cancer Res 1998; 58 ( 23 ): 5310 – 5314.en_US
dc.identifier.citedreferenceTakahashi S, Inaguma S, Sakakibara M, Cho YM, Suzuki S, Ikeda Y, Cui L, Shirai T. DNA methylation in the androgen receptor gene promoter region in rat prostate cancers. Prostate 2002; 52 ( 1 ): 82 – 88.en_US
dc.identifier.citedreferenceKinoshita H, Shi Y, Sandefur C, Meisner LF, Chang C, Choon A, Reznikoff CR, Bova GS, Friedl A, Jarrard DF. Methylation of the androgen receptor minimal promoter silences transcription in human prostate cancer. Cancer Res 2000; 60 ( 13 ): 3623 – 3630.en_US
dc.identifier.citedreferenceNakayama T, Watanabe M, Suzuki H, Toyota M, Sekita N, Hirokawa Y, Mizokami A, Ito H, Yatani R, Shiraishi T. Epigenetic regulation of androgen receptor gene expression in human prostate cancers. Lab Invest 2000; 80 ( 12 ): 1789 – 1796.en_US
dc.identifier.citedreferenceWilson CM, McPhaul MJ. A and B forms of the androgen receptor are present in human genital skin fibroblasts. Proc Natl Acad Sci USA 1994; 91 ( 4 ): 1234 – 1238.en_US
dc.identifier.citedreferenceAhrens‐Fath I, Politz O, Geserick C, Haendler B. Androgen receptor function is modulated by the tissue‐specific AR45 variant. FEBS J 2005; 272 ( 1 ): 74 – 84.en_US
dc.identifier.citedreferenceGuo Z, Qiu Y. A new trick of an old molecule: Androgen receptor splice variants taking the stage?. Int J Biol Sci 2011; 7 ( 6 ): 815 – 822.en_US
dc.identifier.citedreferenceHu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, Han M, Partin AW, Vessella RL, Isaacs WB, Bova GS, Luo J. Ligand‐independent androgen receptor variants derived from splicing of cryptic exons signify hormone‐refractory prostate cancer. Cancer Res 2009; 69 ( 1 ): 16 – 22.en_US
dc.identifier.citedreferenceGuo Z, Yang X, Sun F, Jiang R, Linn DE, Chen H, Kong X, Melamed J, Tepper CG, Kung HJ, Brodie AM, Edwards J, Qiu Y. A novel androgen receptor splice variant is up‐regulated during prostate cancer progression and promotes androgen depletion‐resistant growth. Cancer Res 2009; 69 ( 6 ): 2305 – 2313.en_US
dc.identifier.citedreferenceLiegibel UM, Sommer U, Boercsoek I, Hilscher U, Bierhaus A, Schweikert HU, Nawroth P, Kasperk C. Androgen receptor isoforms AR‐A and AR‐B display functional differences in cultured human bone cells and genital skin fibroblasts. Steroids 2003; 68 ( 14 ): 1179 – 1187.en_US
dc.identifier.citedreferenceRobert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, MacLeod AR. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 2003; 33 ( 1 ): 61 – 65.en_US
dc.identifier.citedreferenceHoffmann MJ, Engers R, Florl AR, Otte AP, Muller M, Schulz WA. Expression changes in EZH2, but not in BMI‐1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer. Cancer Biol Ther 2007; 6 ( 9 ): 1403 – 1412.en_US
dc.identifier.citedreferenceIssa JP, Garcia‐Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM. Phase 1 study of low‐dose prolonged exposure schedules of the hypomethylating agent 5‐aza‐2′‐deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103 ( 5 ): 1635 – 1640.en_US
dc.identifier.citedreferenceCheng JC, Matsen CB, Gonzales FA, Ye W, Greer S, Marquez VE, Jones PA, Selker EU. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst 2003; 95 ( 5 ): 399 – 409.en_US
dc.identifier.citedreferenceJung Y, Park J, Kim TY, Park JH, Jong HS, Im SA, Robertson KD, Bang YJ. Potential advantages of DNA methyltransferase 1 (DNMT1)‐targeted inhibition for cancer therapy. J Mol Med 2007; 85 ( 10 ): 1137 – 1148.en_US
dc.identifier.citedreferenceEdwards J, Krishna NS, Grigor KM, Bartlett JM. Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 2003; 89 ( 3 ): 552 – 556.en_US
dc.identifier.citedreferencevan der Kwast TH, Schalken J, Ruizeveld de Winter JA, van Vroonhoven CC, Mulder E, Boersma W, Trapman J. Androgen receptors in endocrine‐therapy‐resistant human prostate cancer. Int J Cancer 1991; 48 ( 2 ): 189 – 193.en_US
dc.identifier.citedreferenceDavis JN, Wojno KJ, Daignault S, Hofer MD, Kuefer R, Rubin MA, Day ML. Elevated E2F1 inhibits transcription of the androgen receptor in metastatic hormone‐resistant prostate cancer. Cancer Res 2006; 66 ( 24 ): 11897 – 11906.en_US
dc.identifier.citedreferenceEngelmann D, Putzer BM. The dark side of E2F1: In transit beyond apoptosis. Cancer Res 2012; 72 ( 3 ): 571 – 575.en_US
dc.identifier.citedreferenceRhodes DR, Kalyana‐Sundaram S, Mahavisno V, Barrette TR, Ghosh D, Chinnaiyan AM. Mining for regulatory programs in the cancer transcriptome. Nat Genet 2005; 37 ( 6 ): 579 – 583.en_US
dc.identifier.citedreferenceMalhotra S, Lapointe J, Salari K, Higgins JP, Ferrari M, Montgomery K, van de Rijn M, Brooks JD, Pollack JR. A tri‐marker proliferation index predicts biochemical recurrence after surgery for prostate cancer. PLoS ONE 2011; 6 ( 5 ): e20293.en_US
dc.identifier.citedreferenceMcCabe MT, Low JA, Daignault S, Imperiale MJ, Wojno KJ, Day ML. Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res 2006; 66 ( 1 ): 385 – 392.en_US
dc.identifier.citedreferenceMcCabe DC, Caudill MA. DNA methylation, genomic silencing, and links to nutrition and cancer. Nutr Rev 2005; 63 ( 6 Pt 1 ): 183 – 195.en_US
dc.identifier.citedreferenceel‐Deiry WS, Nelkin BD, Celano P, Yen RW, Falco JP, Hamilton SR, Baylin SB. High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc Natl Acad Sci USA 1991; 88 ( 8 ): 3470 – 3474.en_US
dc.identifier.citedreferenceWu CT, Wu CF, Lu CH, Lin CC, Chen WC, Lin PY, Chen MF. Expression and function role of DNA methyltransferase 1 in human bladder cancer. Cancer 2011; 117 ( 22 ): 5221 – 5233.en_US
dc.identifier.citedreferenceChen MF, Chen WC, Chang YJ, Wu CF, Wu CT. Role of DNA methyltransferase 1 in hormone‐resistant prostate cancer. J Mol Med 2010; 88 ( 9 ): 953 – 962.en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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