Upregulated LMO1 in prostate cancer acts as a novel coactivator of the androgen receptor Corrigendum in /10.3892/ijo.2016.3344

Gu,Hui; Liu,Tong; Cai,Xinze; Tong,Yuxin; Li,Yan; Wang,Chunyu; Li,Feng

doi:10.3892/ijo.2015.3195

Upregulated LMO1 in prostate cancer acts as a novel coactivator of the androgen receptor

Corrigendum in: /10.3892/ijo.2016.3344

Authors:
- Hui Gu
- Tong Liu
- Xinze Cai
- Yuxin Tong
- Yan Li
- Chunyu Wang
- Feng Li
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Affiliations: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning, P.R. China
Published online on: October 12, 2015 https://doi.org/10.3892/ijo.2015.3195
Pages: 2181-2187

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Abstract

LMO1, a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the role of LMO1 in human prostate cancer (PCa) is still unknown. Androgen receptor (AR) plays a critical role in the progression of prostate cancer. The activation of AR signaling pathway could be modulated by AR cofactors. In the present study, we discovered that LMO1 could bind to AR and co-localize with AR in the nucleus. In addition, the expression of LMO1 in human PCa tissues was significantly higher than that in benign prostate hyperplasia (BPH) tissues. Moreover, LMO1 appeared to be a novel coactivator to enhance AR transcriptional activities, followed by the elevation of expression of P21 and PSA, downstream targets of AR. Taken together, LMO1 appears to be a coactivator of AR involved in the progression of prostate cancer, and could be a promising molecular target for treating prostate cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yap TA, Zivi A, Omlin A and de Bono JS: The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol. 8:597–610. 2011. View Article : Google Scholar : PubMed/NCBI
3	Zhou Y, Bolton EC and Jones JO: Androgens and androgen receptor signaling in prostate tumorigenesis. J Mol Endocrinol. 54:R15–R29. 2015. View Article : Google Scholar
4	Gelmann EP: Molecular biology of the androgen receptor. J Clin Oncol. 20:3001–3015. 2002. View Article : Google Scholar : PubMed/NCBI
5	Heinlein CA and Chang C: Androgen receptor in prostate cancer. Endocr Rev. 25:276–308. 2004. View Article : Google Scholar : PubMed/NCBI
6	Heemers HV and Tindall DJ: Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 28:778–808. 2007. View Article : Google Scholar : PubMed/NCBI
7	Chmelar R, Buchanan G, Need EF, Tilley W and Greenberg NM: Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer. 120:719–733. 2007. View Article : Google Scholar
8	Boehm T, Foroni L, Kennedy M and Rabbitts TH: The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif. Oncogene. 5:1103–1105. 1990.PubMed/NCBI
9	Jurata LW and Gill GN: Structure and function of LIM domains. Curr Top Microbiol Immunol. 228:75–113. 1998.
10	Dawid IB, Breen JJ and Toyama R: LIM domains: Multiple roles as adapters and functional modifiers in protein interactions. Trends Genet. 14:156–162. 1998. View Article : Google Scholar : PubMed/NCBI
11	Matthews JM, Lester K, Joseph S and Curtis DJ: LIM-domain-only proteins in cancer. Nat Rev Cancer. 13:111–122. 2013. View Article : Google Scholar : PubMed/NCBI
12	Rabbitts TH: LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes. Genes Dev. 12:2651–2657. 1998. View Article : Google Scholar : PubMed/NCBI
13	Liu T, Li Y, Gu H, Zhu G, Li J, Cao L and Li F: p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2). J Biol Chem. 288:3359–3369. 2013. View Article : Google Scholar :
14	Chmelar R, Buchanan G, Need EF, Tilley W and Greenberg NM: Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1. Int J Cancer. 125:2511–2519. 2009. View Article : Google Scholar
15	Berchuck A, Soisson AP, Clarke-Pearson DL, Soper JT, Boyer CM, Kinney RB, McCarty KS Jr and Bast RC Jr: Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: Correlation of antigen expression with metastatic potential. Cancer Res. 49:2091–2095. 1989.PubMed/NCBI
16	Wang C, Li Y, Zhang H, Liu F, Cheng Z, Wang D, Wang G, Xu H, Zhao Y, Cao L, et al: Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis. Oncogene. 33:3473–3484. 2014. View Article : Google Scholar
17	Li Y, Shao Y, Tong Y, Shen T, Zhang J, Li Y, Gu H and Li F: Nucleo-cytoplasmic shuttling of PAK4 modulates β-catenin intracellular translocation and signaling. Biochim Biophys Acta. 1823:465–475. 2012. View Article : Google Scholar
18	Riegman PH, Vlietstra RJ, van der Korput JA, Brinkmann AO and Trapman J: The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol Endocrinol. 5:1921–1930. 1991. View Article : Google Scholar : PubMed/NCBI
19	Lu S, Liu M, Epner DE, Tsai SY and Tsai MJ: Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Mol Endocrinol. 13:376–384. 1999. View Article : Google Scholar : PubMed/NCBI
20	Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO and Trapman J: Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem. 271:6379–6388. 1996. View Article : Google Scholar : PubMed/NCBI
21	Taplin ME and Balk SP: Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem. 91:483–490. 2004. View Article : Google Scholar : PubMed/NCBI
22	Debes JD and Tindall DJ: Mechanisms of androgen-refractory prostate cancer. N Engl J Med. 351:1488–1490. 2004. View Article : Google Scholar : PubMed/NCBI
23	Boehm T, Baer R, Lavenir I, Forster A, Waters JJ, Nacheva E and Rabbitts TH: The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 7:385–394. 1988.PubMed/NCBI
24	Boehm T, Foroni L, Kaneko Y, Perutz MF and Rabbitts TH: The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc Natl Acad Sci USA. 88:4367–4371. 1991. View Article : Google Scholar : PubMed/NCBI
25	Van Vlierberghe P, van Grotel M, Beverloo HB, Lee C, Helgason T, Buijs-Gladdines J, Passier M, van Wering ER, Veerman AJ, Kamps WA, et al: The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia. Blood. 108:3520–3529. 2006. View Article : Google Scholar : PubMed/NCBI
26	Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, et al: Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 1:75–87. 2002. View Article : Google Scholar : PubMed/NCBI
27	Tremblay M, Tremblay CS, Herblot S, Aplan PD, Hébert J, Perreault C and Hoang T: Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1 oncogenes. Genes Dev. 24:1093–1105. 2010. View Article : Google Scholar : PubMed/NCBI
28	Neale GA, Rehg JE and Goorha RM: Disruption of T-cell differentiation precedes T-cell tumor formation in LMO-2 (rhombotin-2) transgenic mice. Leukemia. 11(Suppl 3): 289–290. 1997.PubMed/NCBI
29	Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, et al: Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. 469:216–220. 2011. View Article : Google Scholar
30	Aoyama M, Ozaki T, Inuzuka H, Tomotsune D, Hirato J, Okamoto Y, Tokita H, Ohira M and Nakagawara A: LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma. Cancer Res. 65:4587–4597. 2005. View Article : Google Scholar : PubMed/NCBI
31	Montañez-Wiscovich ME, Seachrist DD, Landis MD, Visvader J, Andersen B and Keri RA: LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression. Oncogene. 28:3608–3618. 2009. View Article : Google Scholar : PubMed/NCBI
32	Wang N, Lin KK, Lu Z, Lam KS, Newton R, Xu X, Yu Z, Gill GN and Andersen B: The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene. 26:6431–6441. 2007. View Article : Google Scholar : PubMed/NCBI
33	Ma S, Guan XY, Beh PS, Wong KY, Chan YP, Yuen HF, Vielkind J and Chan KW: The significance of LMO2 expression in the progression of prostate cancer. J Pathol. 211:278–285. 2007. View Article : Google Scholar
34	Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI
35	Wang J and Walsh K: Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation. Science. 273:359–361. 1996. View Article : Google Scholar : PubMed/NCBI
36	Lu S, Tsai SY and Tsai MJ: Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells. Endocrinology. 140:5054–5059. 1999.PubMed/NCBI
37	Omar EA, Behlouli H, Chevalier S and Aprikian AG: Relationship of p21(WAF-I) protein expression with prognosis in advanced prostate cancer treated by androgen ablation. Prostate. 49:191–199. 2001. View Article : Google Scholar : PubMed/NCBI
38	Fizazi K, Martinez LA, Sikes CR, Johnston DA, Stephens LC, McDonnell TJ, Logothetis CJ, Trapman J, Pisters L, et al: The association of p21^(WAF-1/CIP1) with progression to androgen-independent prostate cancer. Clin Cancer Res. 8:775–781. 2002.PubMed/NCBI
39	Gorospe M, Cirielli C, Wang X, Seth P, Capogrossi MC and Holbrook NJ: p21^Waf1/Cip1 protects against p53-mediated apoptosis of human melanoma cells. Oncogene. 14:929–935. 1997. View Article : Google Scholar : PubMed/NCBI
40	Gittes RF: Carcinoma of the prostate. N Engl J Med. 324:236–245. 1991. View Article : Google Scholar : PubMed/NCBI