LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner
作者： Holly B Kramer , Chun-Fui Lai , Hetal Patel , Manikandan Periyasamy , Meng-Lay Lin
DOI: 10.1093/NAR/GKV948
关键词:
摘要: Liver receptor homologue 1 (LRH-1) is an orphan nuclear that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 CRC, we undertook global expression profiling following siRNA-mediated knockdown HCT116 cells, which require for HT29 does not regulate growth. Interestingly, cell cycle inhibitor p21 (CDKN1A) was regulated cells. regulation observed where p53 mutated. dependence confirmed with siRNA, while LRH-1-regulation evident cells had deleted. We demonstrate LRH-1-mediated involve altered protein or phosphorylation, show inhibits recruitment to promoter, likely through a mechanism involving chromatin remodelling. Our study suggests important role CRC retain wild-type p53.
oup.com
core.ac.uk
imperial.ac.uk
paperity.org
oxfordjournals.org 参考文章(77)
Joung Woul Kim, Noel Peng, William E. Rainey, Bruce R. Carr, George R. Attia, Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells. The Journal of Clinical Endocrinology and Metabolism. ,vol. 89, pp. 3042- 3047 ,(2004) , 10.1210/JC.2003-031599
L Buluwela, J Pike, D Mazhar, T Kamalati, S M Hart, R Al-Jehani, H Yahaya, N Patel, N Sarwarl, D A Heathcote, O Schwickerath, F Phoenix, R Hill, E Aboagye, S Shousha, J Waxman, N R Lemoine, A Zelent, R C Coombes, S Ali, Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-α and the transcriptional repressor PLZF Gene Therapy. ,vol. 12, pp. 452- 460 ,(2005) , 10.1038/SJ.GT.3302421
M. Olivier, M. Hollstein, P. Hainaut, TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use Cold Spring Harbor Perspectives in Biology. ,vol. 2, ,(2010) , 10.1101/CSHPERSPECT.A001008
Da Wei Huang, Brad T. Sherman, Richard A. Lempicki, Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists Nucleic Acids Research. ,vol. 37, pp. 1- 13 ,(2009) , 10.1093/NAR/GKN923
Wafik S El-Deiry, J Wade Harper, Patrick M O'Connor, Victor E Velculescu, Christine E Canman, Joany Jackman, Jennifer A Pietenpol, Burrell M, David E Hill, Yisong Wang, Klas G Wiman, W Edward Mercer, Michael B Kastan, Kurt W Kohn, Stephen J Elledge, Kenneth W Kinzler, Bert Vogelstein, WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis Cancer Research. ,vol. 54, pp. 1169- 1174 ,(1994)
Jean-Sébastien Annicotte, Carine Chavey, Nadège Servant, Jacques Teyssier, Aurélie Bardin, Anne Licznar, Eric Badia, Pascal Pujol, Françoise Vignon, Thierry Maudelonde, Gwendal Lazennec, Vincent Cavailles, Lluis Fajas, The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene Oncogene. ,vol. 24, pp. 8167- 8175 ,(2005) , 10.1038/SJ.ONC.1208950
Allison E. Falender, Rainer Lanz, Daniel Malenfant, Luc Belanger, JoAnne S. Richards, Differential expression of steroidogenic factor-1 and FTF/LRH-1 in the rodent ovary Endocrinology. ,vol. 144, pp. 3598- 3610 ,(2003) , 10.1210/EN.2002-0137
Eric R. Fearon, Molecular Genetics of Colorectal Cancer Annual Review of Pathology: Mechanisms of Disease. ,vol. 6, pp. 479- 507 ,(2011) , 10.1146/ANNUREV-PATHOL-011110-130235
Bert Vogelstein, Christos Paraskeva, Antonette C. Preisinger, J. K V Willson, Suzanne J. Baker, Sanford D Markowitz, Stanley Hamilton, J. M. Jessup, p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Research. ,vol. 50, pp. 7717- 7722 ,(1990)
Da Wei Huang, Brad T Sherman, Richard A Lempicki, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols. ,vol. 4, pp. 44- 57 ,(2009) , 10.1038/NPROT.2008.211