ArticleThe Prostate2012
Androgens repress expression of the F-box protein Skp2 via p107 dependent and independent mechanisms in LNCaP prostate cancer cells.
Article in The Prostate, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.Biomedicines · 2023Review
- Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- High-dose-androgen-induced autophagic cell death to suppress the Enzalutamide-resistant prostate cancer growth via altering the circRNA-BCL2/miRNA-198/AMBRA1 signaling.Cell death discovery · 2022Article
- Discovery proteomics defines androgen-regulated glycoprotein networks in prostate cancer cells, as well as putative biomarkers of prostatic diseases.Scientific reports · 2021Article
- Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress.Cell reports · 2020Article
- Article
- Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions.Cancers · 2017Review
- Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation.Molecular and cellular endocrinology · 2017Article
- Androgen Receptor Tumor Suppressor Function Is Mediated by Recruitment of Retinoblastoma Protein.Cell reports · 2016Article
- Article
- Skp2 and its emerging role in the pathogenesis of systemic malignancies besides breast carcinomas.Frontiers in oncology · 2012Article
- Skp2: a novel potential therapeutic target for prostate cancer.Biochimica et biophysica acta · 2012Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAndrogens control homeostasis of the normal prostate and growth of prostate cancer (PCa) through the androgen receptor (AR) by regulating gene networks involving in cell proliferation, differentiation, and survival. We demonstrated previously that expression of Skp2, a key protein regulating cell entry into the S phase, is inhibited by androgens in an AR-dependent manner (Oncogene, 2004; 23(12): 2161-2176). However, the underlying mechanism of this regulation is unknown.
methodsUsing the LNCaP PCa cell line as a working model, the effect of androgens on the expression of Skp2 was examined by Western and Northern blot analyses. Cell cycle was measured by fluorescence-activated cell sorting (FACS). Gene transfection was performed by electroporation to manipulate the expression levels of proteins studied.
resultsAt physiological levels androgens markedly repressed Skp2 expression but slightly induced Skp2 expression at subphysiological levels. Androgens modestly decreased the stability of the Skp2 protein. Androgenic repression of Skp2 expression was completely abolished by E1A-mediated inactivation of pocket proteins including RB, p130, and p107. Moreover, ectopic expression of p107 inhibited Skp2 expression, and silencing of p107 partially blocked androgenic repression of Skp2.
conclusionsOur data indicate that androgens repress Skp2 expression via p107-dependent and -independent pathways in PCa cells. These regulatory mechanisms may be targeted for the development of new therapeutics of androgen-refractory PCa.
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