ArticleOncogene2004
Deregulation of the Rho GTPase, Rac1, suppresses cyclin-dependent kinase inhibitor p21(CIP1) levels in androgen-independent human prostate cancer cells.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The role of microRNA in castration-resistant prostate cancer.Urologic oncology · 2014Pooled it
- Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis.Cancer biology & therapy · 2017Trial
- Article
- MicroRNAs in treatment-induced neuroendocrine differentiation in prostate cancer.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Phorbol myristate acetate suppresses breast cancer cell growth via down-regulation of P-Rex1 expression.Protein & cell · 2016Article
- Infectivity and insertional mutagenesis of endogenous retrovirus in autoimmune NZB and B/W mice.The Journal of general virology · 2015Article
- Targeting geranylgeranylation reduces adrenal gland tumor burden in a murine model of prostate cancer metastasis.Clinical & experimental metastasis · 2015Article
- Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.Oncotarget · 2015Article
- Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion.BMC cancer · 2014Article
- Rac1-dependent lamellipodial motility in prostate cancer PC-3 cells revealed by optogenetic control of Rac1 activity.PloS one · 2014Article
- The microRNA -23b/-27b cluster suppresses the metastatic phenotype of castration-resistant prostate cancer cells.PloS one · 2012Article
- WAVE regulatory complex activation by cooperating GTPases Arf and Rac1.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Epigenetic regulation of phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger 1 gene expression in prostate cancer cells.The Journal of biological chemistry · 2011Article
- Differential roles of Smad2 and Smad3 in the regulation of TGF-β1-mediated growth inhibition and cell migration in pancreatic ductal adenocarcinoma cells: control by Rac1.Molecular cancer · 2011Article
- Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.Endocrine-related cancer · 2011Article
- CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells.Cancer research · 2011Article
- Activation of Rac1 is closely related to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo.Molecular endocrinology (Baltimore, Md.) · 2010Article
- p66Shc--a longevity redox protein in human prostate cancer progression and metastasis : p66Shc in cancer progression and metastasis.Cancer metastasis reviews · 2010Review
- Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis.Oncogene · 2009Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Abnormally suppressed levels of cyclin-dependent kinase inhibitors (CKIs) are associated with aggressive androgen-independent prostate cancer and contribute to uncontrolled proliferation. The androgen-independent human prostate cancer cell lines, LNCaP-104R1, ALVA31 and PC-3, express low levels of the CKI, p21(CIP1), compared to the less-malignant, androgen-dependent LNCaP cells. We investigated the mechanism underlying this suppression by examining the role of Rho GTPases, signaling proteins that play important roles in cell cycle progression, at least in part through regulation of CKIs. Inhibition of Rac1 induced p21 expression in androgen-independent lines but had no effect on the higher p21 levels characteristic of LNCaP cells. This induction of p21 was functionally significant as evidenced by inhibition of cyclin-dependent kinase 2 activity and decreased cell proliferation. Conversely, overexpression of constitutively active Rac1 suppressed the higher p21 levels seen in LNCaP cells. Thus, Rac1 activity is both necessary and sufficient for suppression of p21 in prostate cancer cells. Furthermore, Rac1 activity was significantly higher in all three androgen-independent cell lines compared to LNCaP cells. Thus in three models of aggressive human prostate cancer, hyperactivity of Rac1 corresponds to suppressed levels of p21. These results are unique in describing a role for Rac1 in p21 regulation and may implicate the Rac1 signaling pathway as a potential therapeutic target for controlling prostate cancer cell growth following progression to androgen independence.
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