Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The androgen receptor (AR), a steroid receptor family member, is a ligand-dependent transcription factor that has an integral role in normal prostate development. Alterations in AR-mediated activity can result in abnormal gene expression, dysregulated cell growth and prostate cancer. Coregulator proteins that interact with AR to influence activity and specificity of the AR-response may also have an important role in prostate cancer progression. Since the NH(2)-terminal domain (NTD) of AR encodes the ligand-independent activation function (AF)-1, this domain is incompatible with conventional yeast two-hybrid systems. Therefore, we have used the Tup1 repressed transactivator (RTA) system, which exploits the intrinsic transactivation properties of AR.NTD, for identification of novel AR-interacting proteins. Using this system, cyclin G-associated kinase (GAK) was identified as an AR interacting protein, and GST pull-down assays were used to confirm the interaction. GAK was shown to enhance the AF-1 function of AR activity in a ligand-dependent manner. Additionally, GAK enhanced the AR transcriptional response even at low concentrations of androgens, which is relevant to AR activity in androgen-independent prostate cancer. Finally, neo-adjuvant hormone therapy (NHT) tissue microarray analysis demonstrated that GAK expression increased significantly with prostate cancer progression to androgen independence, which suggests a prognostic role for GAK in advanced disease.
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PMID:Cyclin G-associated kinase: a novel androgen receptor-interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer. 1616 Oct 52

Prostate cancer is the most common illness affecting men worldwide. Although much progress has been made in the study of prostate cancer prevention and treatment, less attention has been paid to the molecular mechanism of the disease. The molecular arrangement by which atractylenolide II (ATR II) induces human prostate cancer cytotoxicity was comprehensively examined in the present study. As indicated by the results, ATR II could inhibit prostate cancer cell proliferation and promote DU145 and LNCaP cell apoptosis through induced G2/M cell cycle arrest. The cell apoptosis process induced by ATR II in both DU145 and LNCaP cells was associated with its ability to inhibit androgen receptor (AR) with overexpression of protein inhibitor of activated STAT-1 (PIAS1) and the repression of Janus kinase (Jak2) signaling pathways. The data from the present study demonstrated the antitumor effects and the potential pharmacological application of ATR II as an efficient drug for prostate cancer treatment.
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PMID:Atractylenolide II Induces Apoptosis of Prostate Cancer Cells through Regulation of AR and JAK2/STAT3 Signaling Pathways. 3054 41