scholarly journals The Interplay of AMP-Activated Protein Kinase and Androgen Receptor in Prostate Cancer Cells

2014 ◽  
Vol 229 (6) ◽  
pp. 688-695 ◽  
Author(s):  
Min Shen ◽  
Zhen Zhang ◽  
Manohar Ratnam ◽  
Q. Ping Dou
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Amp Activated Protein Kinase

T-LAK cell-originated protein kinase (TOPK) enhances androgen receptor splice variant (ARv7) and drives androgen-independent growth in prostate cancer

2020 ◽  
Author(s):  
Lama Alhawas ◽  
Karishma S Amin ◽  
Bharath Salla ◽  
Partha P Banerjee
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Androgen Independence ◽  
Androgen Synthesis ◽  
Lak Cell ◽  
Androgen Independent ◽  
Constitutively Active

Abstract Despite impressive advances in the treatment of prostate cancer with various efficacious inhibitors along the androgen/androgen receptor axis, eventual development of incurable metastatic Castration-Resistant Prostate Cancer (mCRPC) is inevitable and remains a major clinical challenge. Constitutively active androgen receptor (AR) spliced variants have emerged as primary means of resistance to anti-androgens and androgen synthesis inhibitors. The alternatively spliced AR variant, ARv7, has attracted significant interest due to its constitutively active status in CRPC that drives androgen-independence. Factors that are involved in regulating ARv7 levels in CRPC are not clearly known. We recently demonstrated that a protein kinase, T-LAK cell-originated protein kinase (TOPK) level correlates with the aggressiveness of prostate cancer and its invasive behavior. In this study we investigated whether TOPK plays a role in driving androgen-independence in prostate cancer cells. Our data demonstrate that TOPK overexpression in androgen-dependent LNCaP and VCaP induces ARv7 and drives androgen-independent growth. On the other hand, pharmacological inhibition of TOPK in androgen-independent LNCaP95 and 22Rv1 represses AR transactivation, and AR stability. In summary, this study illustrates a direct role of TOPK in regulating ARv7 and driving androgen-independence in prostate cancer cells.

scholarly journals Mitogen-Activated Protein Kinase Kinase Kinase 1 Activates Androgen Receptor-Dependent Transcription and Apoptosis in Prostate Cancer

1999 ◽  
Vol 19 (7) ◽  
pp. 5143-5154 ◽  
Author(s):  
Maria T. Abreu-Martin ◽  
Ajai Chari ◽  
Andrew A. Palladino ◽  
Noah A. Craft ◽  
Charles L. Sawyers
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Signaling ◽  
Prostate Cancer Cells ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

ABSTRACT Mitogen-activated protein (MAP) kinases phosphorylate the estrogen receptor and activate transcription from estrogen receptor-regulated genes. Here we examine potential interactions between the MAP kinase cascade and androgen receptor-mediated gene regulation. Specifically, we have studied the biological effects of mitogen-activated protein kinase kinase kinase 1 (MEKK1) expression in prostate cancer cells. Our findings demonstrate that expression of constitutively active MEKK1 induces apoptosis in androgen receptor-positive but not in androgen receptor-negative prostate cancer cells. Reconstitution of the androgen receptor signaling pathway in androgen receptor-negative prostate cancer cells restores MEKK1-induced apoptosis. MEKK1 also stimulates the transcriptional activity of the androgen receptor in the presence or absence of ligand, whereas a dominant negative mutant of MEKK1 impairs activation of the androgen receptor by androgen. These studies demonstrate an unanticipated link between MEKK1 and hormone receptor signaling and have implications for the molecular basis of hormone-independent prostate cancer growth.

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