Down‐regulation of calcium/calmodulin‐dependent protein kinase kinase 2 by androgen deprivation induces castration‐resistant prostate cancer
dc.contributor.author | Shima, Takashi | en_US |
dc.contributor.author | Mizokami, Atsushi | en_US |
dc.contributor.author | Miyagi, Toru | en_US |
dc.contributor.author | Kawai, Keiichi | en_US |
dc.contributor.author | Izumi, Kouji | en_US |
dc.contributor.author | Kumaki, Misako | en_US |
dc.contributor.author | Ofude, Mitsuo | en_US |
dc.contributor.author | Zhang, Jian | en_US |
dc.contributor.author | Keller, Evan T. | en_US |
dc.contributor.author | Namiki, Mikio | en_US |
dc.date.accessioned | 2012-11-07T17:04:37Z | |
dc.date.available | 2014-02-03T16:21:43Z | en_US |
dc.date.issued | 2012-12-01 | en_US |
dc.identifier.citation | Shima, Takashi; Mizokami, Atsushi; Miyagi, Toru; Kawai, Keiichi; Izumi, Kouji; Kumaki, Misako; Ofude, Mitsuo; Zhang, Jian; Keller, Evan T.; Namiki, Mikio (2012). "Down‐regulation of calcium/calmodulin‐dependent protein kinase kinase 2 by androgen deprivation induces castration‐resistant prostate cancer ." The Prostate 72(16): 1789-1801. <http://hdl.handle.net/2027.42/94268> | en_US |
dc.identifier.issn | 0270-4137 | en_US |
dc.identifier.issn | 1097-0045 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/94268 | |
dc.description.abstract | BACKGROUND Conversion into androgen‐hypersensitive state and adaptation to the low concentration of androgen during ADT cause relapse of prostate cancer (PCa). It is important to identify differentially expressed genes between PCa and normal prostate tissues and to reveal the function of these genes that are involved in progression of PCa. METHODS We performed cDNA microarray analysis to identify differentially expressed genes, calcium/calmodulin‐dependent protein kinase kinase 2 (CAMKK2). Immunohistochemical analysis was conducted to investigate the relationship between the CAMKK2 expression level and prognosis. The function of CAMKK2 was assessed by generating CAMKK2 overexpressed LNCaP cells and by knockdown of CAMKK2. RESULTS We identified CAMKK2 overexpressed six times in PCa more than normal prostate by cDNA microarray analysis. Immunohistochemical analysis of CAMKK2 protein showed that CAMKK2 protein was expressed more in PCa than normal tissue. However, the expression in the high‐grade PCa diminished. Moreover, the narrowness of CAMKK2‐positive area before ADT was a poor prognostic factor. Androgen‐deprivation treatment from the medium in which LNCaP cells were cultured in the presence of 10 nM DHT repressed CAMKK2 expression. CAMKK2 overexpressed LNCaP cells (LNCaP/GFP‐CAMKK2) attenuated androgen‐sensitivity. Tumorigenesis of LNCaP/GFP‐CAMKK2 cells in male SCID mice was decreased compared with control cells irrespective of castration. Finally, knockdown of CAMKK2 mRNA in LNCaP cells induced androgen‐hypersensitivity and stimulated LNCaP cell proliferation. CONCLUSIONS Induction of androgen‐hypersensitivity after ADT may be involved in down‐regulation of CAMKK2. This result may provide new therapeutic approach to keep androgen‐sensitivity of PCa after ADT. Prostate 72:1789–1801, 2012. © 2012 Wiley Periodicals, Inc. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | CAMKK2 | en_US |
dc.subject.other | AMPK | en_US |
dc.subject.other | Androgen‐Hypersensitivity | en_US |
dc.subject.other | Prostate Cancer | en_US |
dc.title | Down‐regulation of calcium/calmodulin‐dependent protein kinase kinase 2 by androgen deprivation induces castration‐resistant prostate cancer | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Departments of Urology and Pathology, University of Michigan, Ann Arbor, Minnesota | en_US |
dc.contributor.affiliationother | Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan | en_US |
dc.contributor.affiliationother | Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, 13‐1 Takaramachi, Kanazawa, Ishikawa 920‐8640, Japan. | en_US |
dc.contributor.affiliationother | Guangxi Medical University, Pharmacology and Biomedical Sciences, Guangxi, China | en_US |
dc.contributor.affiliationother | Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan | en_US |
dc.identifier.pmid | 22549914 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/94268/1/22533_ftp.pdf | |
dc.identifier.doi | 10.1002/pros.22533 | en_US |
dc.identifier.source | The Prostate | en_US |
dc.identifier.citedreference | Schuur ER, Henderson GA, Kmetec LA, Miller JD, Lamparski HG, Henderson DR. Prostate‐specific antigen expression is regulated by an upstream enhancer. J Biol Chem 1996; 271 ( 12 ): 7043 – 7051. | en_US |
dc.identifier.citedreference | Mizokami A, Koh E, Izumi K, Narimoto K, Takeda M, Honma S, Dai J, Keller E, Namiki M. Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of T and DHT from DHEA. Endocr Relat Cancer 2009; 16: 1139 – 1155. | en_US |
dc.identifier.citedreference | Veldscholte J, Voorhorst‐Ogink MM, Bolt‐de Vries J, van Rooij HC, Trapman J, Mulder E. Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: High affinity for progestagenic and estrogenic steroids. Biochim Biophys Acta 1990; 1052 ( 1 ): 187 – 194. | en_US |
dc.identifier.citedreference | Duff J, McEwan IJ. Mutation of histidine 874 in the androgen receptor ligand‐binding domain leads to promiscuous ligand activation and altered p160 coactivator interactions. Mol Endocrinol 2005; 19 ( 12 ): 2943 – 2954. | en_US |
dc.identifier.citedreference | Koivisto P, Kononen J, Palmberg C, Tammela T, Hyytinen E, Isola J, Trapman J, Cleutjens K, Noordzij A, Visakorpi T, Kallioniemi OP. Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res 1997; 57 ( 2 ): 314 – 319. | en_US |
dc.identifier.citedreference | Steinkamp MP, O'Mahony OA, Brogley M, Rehman H, Lapensee EW, Dhanasekaran S, Hofer MD, Kuefer R, Chinnaiyan A, Rubin MA, Pienta KJ, Robins DM. Treatment‐dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res 2009; 69 ( 10 ): 4434 – 4442. | en_US |
dc.identifier.citedreference | Kang Z, Janne OA, Palvimo JJ. Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Mol Endocrinol 2004; 18 ( 11 ): 2633 – 2648. | en_US |
dc.identifier.citedreference | Debes JD, Comuzzi B, Schmidt LJ, Dehm SM, Culig Z, Tindall DJ. p300 regulates androgen receptor‐independent expression of prostate‐specific antigen in prostate cancer cells treated chronically with interleukin‐6. Cancer Res 2005; 65 ( 13 ): 5965 – 5973. | en_US |
dc.identifier.citedreference | Holzbeierlein J, Lal P, LaTulippe E, Smith A, Satagopan J, Zhang L, Ryan C, Smith S, Scher H, Scardino P, Reuter V, Gerald WL. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen‐responsive genes and mechanisms of therapy resistance. Am J Pathol 2004; 164 ( 1 ): 217 – 227. | en_US |
dc.identifier.citedreference | Cooper CS, Campbell C, Jhavar S. Mechanisms of Disease: Biomarkers and molecular targets from microarray gene expression studies in prostate cancer. Nat Clin Pract Urol 2007; 4 ( 12 ): 677 – 687. | en_US |
dc.identifier.citedreference | Tamura K, Furihata M, Tsunoda T, Ashida S, Takata R, Obara W, Yoshioka H, Daigo Y, Nasu Y, Kumon H, Konaka H, Namiki M, Tozawa K, Kohri K, Tanji N, Yokoyama M, Shimazui T, Akaza H, Mizutani Y, Miki T, Fujioka T, Shuin T, Nakamura Y, Nakagawa H. Molecular features of hormone‐refractory prostate cancer cells by genome‐wide gene expression profiles. Cancer Res 2007; 67 ( 11 ): 5117 – 5125. | en_US |
dc.identifier.citedreference | Sorensen KD, Orntoft TF. Discovery of prostate cancer biomarkers by microarray gene expression profiling. Expert Rev Mol Diagn 2010; 10 ( 1 ): 49 – 64. | en_US |
dc.identifier.citedreference | Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004; 101 ( 3 ): 811 – 816. | en_US |
dc.identifier.citedreference | Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar‐Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419 ( 6907 ): 624 – 629. | en_US |
dc.identifier.citedreference | Frigo DE, Howe MK, Wittmann BM, Brunner AM, Cushman I, Wang Q, Brown M, Means AR, McDonnell DP. CaM kinase kinase beta‐mediated activation of the growth regulatory kinase AMPK is required for androgen‐dependent migration of prostate cancer cells. Cancer Res 2011; 71 ( 2 ): 528 – 537. | en_US |
dc.identifier.citedreference | Massie CE, Lynch A, Ramos‐Montoya A, Boren J, Stark R, Fazli L, Warren A, Scott H, Madhu B, Sharma N, Bon H, Zecchini V, Smith DM, Denicola GM, Mathews N, Osborne M, Hadfield J, Macarthur S, Adryan B, Lyons SK, Brindle KM, Griffiths J, Gleave ME, Rennie PS, Neal DE, Mills IG. The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. EMBO J 2011; 30 ( 13 ): 2719 – 2733. | en_US |
dc.identifier.citedreference | Mizokami A, Gotoh A, Yamada H, Keller ET, Matsumoto T. Tumor necrosis factor‐alpha represses androgen sensitivity in the LNCaP prostate cancer cell line. J Urol 2000; 164 ( 3 Pt 1 ): 800 – 805. | en_US |
dc.identifier.citedreference | Izumi K, Mizokami A, Li YQ, Narimoto K, Sugimoto K, Kadono Y, Kitagawa Y, Konaka H, Koh E, Keller ET, Namiki M. Tranilast inhibits hormone refractory prostate cancer cell proliferation and suppresses transforming growth factor beta1‐associated osteoblastic changes. Prostate 2009; 69 ( 11 ): 1222 – 1234. | en_US |
dc.identifier.citedreference | Mizokami A, Saiga H, Matsui T, Mita T, Sugita A. Regulation of androgen receptor by androgen and epidermal growth factor in a human prostatic cancer cell line, LNCaP. Endocrinol Jpn 1992; 39 ( 3 ): 235 – 243. | en_US |
dc.identifier.citedreference | Li Y, Mizokami A, Izumi K, Narimoto K, Shima T, Zhang J, Dai J, Keller ET, Namiki M. CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer. Prostate 2010; 70 ( 1 ): 48 – 60. | en_US |
dc.identifier.citedreference | Sonnenschein C, Olea N, Pasanen ME, Soto AM. Negative controls of cell proliferation: Human prostate cancer cells and androgens. Cancer Res 1989; 49 ( 13 ): 3474 – 3481. | en_US |
dc.identifier.citedreference | Neuwirt H, Puhr M, Cavarretta IT, Mitterberger M, Hobisch A, Culig Z. Suppressor of cytokine signalling‐3 is up‐regulated by androgen in prostate cancer cell lines and inhibits androgen‐mediated proliferation and secretion. Endocr Relat Cancer 2007; 14 ( 4 ): 1007 – 1019. | en_US |
dc.identifier.citedreference | Pelley RP, Chinnakannu K, Murthy S, Strickland FM, Menon M, Dou QP, Barrack ER, Reddy GP. Calmodulin‐androgen receptor (AR) interaction: Calcium‐dependent, calpain‐mediated breakdown of AR in LNCaP prostate cancer cells. Cancer Res 2006; 66 ( 24 ): 11754 – 11762. | en_US |
dc.identifier.citedreference | Sivanandam A, Murthy S, Chinnakannu K, Bai VU, Kim SH, Barrack ER, Menon M, Reddy GP. Calmodulin protects androgen receptor from calpain‐mediated breakdown in prostate cancer cells. J Cell Physiol 2011; 226 ( 7 ): 1889 – 1896. | en_US |
dc.identifier.citedreference | Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG. Calmodulin‐dependent protein kinase kinase‐beta is an alternative upstream kinase for AMP‐activated protein kinase. Cell Metab 2005; 2 ( 1 ): 9 – 19. | en_US |
dc.identifier.citedreference | Zhou J, Huang W, Tao R, Ibaragi S, Lan F, Ido Y, Wu X, Alekseyev YO, Lenburg ME, Hu GF, Luo Z. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene 2009; 28 ( 18 ): 1993 – 2002. | en_US |
dc.identifier.citedreference | Zhou J, Yang Z, Tsuji T, Gong J, Xie J, Chen C, Li W, Amar S, Luo Z. LITAF and TNFSF15, two downstream targets of AMPK, exert inhibitory effects on tumor growth. Oncogene 2011; 30 ( 16 ): 1892 – 1900. | en_US |
dc.identifier.citedreference | Shackelford DB, Shaw RJ. The LKB1‐AMPK pathway: Metabolism and growth control in tumour suppression. Nat Rev Cancer 2009; 9 ( 8 ): 563 – 575. | en_US |
dc.identifier.citedreference | Park HU, Suy S, Danner M, Dailey V, Zhang Y, Li H, Hyduke DR, Collins BT, Gagnon G, Kallakury B, Kumar D, Brown ML, Fornace A, Dritschilo A, Collins SP. AMP‐activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther 2009; 8 ( 4 ): 733 – 741. | en_US |
dc.identifier.citedreference | Hadad SM, Baker L, Quinlan PR, Robertson KE, Bray SE, Thomson G, Kellock D, Jordan LB, Purdie CA, Hardie DG, Fleming S, Thompson AM. Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer 2009; 9: 307. | en_US |
dc.identifier.citedreference | Sun W, Wang L, Shyy JY, Sun W. Abstract 1914: Atorvastatin activates CaMKK‐beta as an upstream kinase of AMPK in endothelium. Circulation 2008; 118: S_404. | en_US |
dc.identifier.citedreference | Zheng X, Cui XX, Gao Z, Zhao Y, Lin Y, Shih WJ, Huang MT, Liu Y, Rabson A, Reddy B, Yang CS, Conney AH. Atorvastatin and celecoxib in combination inhibits the progression of androgen‐dependent LNCaP xenograft prostate tumors to androgen independence. Cancer Prev Res (Phila) 2010; 3 ( 1 ): 114 – 124. | en_US |
dc.identifier.citedreference | Fujimoto N, Miyamoto H, Mizokami A, Harada S, Nomura M, Ueta Y, Sasaguri T, Matsumoto T. Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone‐resistance of prostate cancer cells. Cancer Invest 2007; 25 ( 1 ): 32 – 37. | en_US |
dc.identifier.citedreference | Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61 ( 4 ): 212 – 236. | en_US |
dc.identifier.citedreference | Hoimes CJ, Kelly WK. Redefining hormone resistance in prostate cancer. Ther Adv Med Oncol 2010; 2 ( 2 ): 107 – 123. | en_US |
dc.identifier.citedreference | Taplin ME, Balk SP. Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem 2004; 91 ( 3 ): 483 – 490. | en_US |
dc.identifier.citedreference | Nishiyama T, Hashimoto Y, Takahashi K. The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clin Cancer Res 2004; 10 ( 21 ): 7121 – 7126. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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