1. Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer
- Author
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Per-Anders Abrahamsson, Jenny L. Persson, Martuza Sarwar, and Sabina Sandberg
- Subjects
Male ,medicine.medical_specialty ,Urology ,urologic and male genital diseases ,Metastasis ,chemistry.chemical_compound ,Prostate cancer ,Prostate ,Internal medicine ,Cell Line, Tumor ,LNCaP ,medicine ,Cyclic AMP ,Humans ,Cyclic adenosine monophosphate ,Neoplasm Metastasis ,Protein kinase A ,Forskolin ,business.industry ,Gene Expression Profiling ,Colforsin ,Prostatic Neoplasms ,Prostate-Specific Antigen ,medicine.disease ,Cyclic AMP-Dependent Protein Kinases ,Cyclic Nucleotide Phosphodiesterases, Type 4 ,Androgen receptor ,Gene Expression Regulation, Neoplastic ,Endocrinology ,medicine.anatomical_structure ,Oncology ,chemistry ,Microscopy, Fluorescence ,Receptors, Androgen ,Cancer research ,business ,Rolipram ,Signal Transduction - Abstract
OBJECTIVES: In the present study, we investigated whether the cyclic adenosine monophosphate (cAMP)-activated protein kinase A (PKA) pathway may regulate the expression of AR and prostate-specific antigen (PSA) and whether there is a correlation between the expression of cAMP/PKA-associated genes and androgen receptors (ARs) in patients with prostate cancer (CaP). MATERIALS AND METHODS: The functional studies were performed in LNCaP and PC3 cell lines. Data on the mRNA expression of sets of genes in human clinical samples, including prostate tissues from organ donors, prostate primary cancer, and metastatic cancer, were extracted from the National Center for Biotechnology Informations Gene Expression Omnibus (GEO) database. Statistical tests were applied. RESULTS: We showed that elevated levels of cAMP/PKA pathways induced an increased expression of AR and PSA proteins in LNCaP cells in the absence of androgen. A cAMP-associated phosphodiesterase-4 (PDE4) inhibitor, Rolipram induced an up-regulation in AR expression, whereas a cAMP enhancer, Forskolin increased PSA level without affecting AR expression. Forskolin treatment increased the level of PKA R1α in LNCaP cells, but remarkably inhibited R1α expression in aggressive PC3 cells. In patients with CaP, we found that the expression of genes encoding R1α and phosphodiesterase-4B was statistically significantly lower in the metastatic specimens than that in the primary CaP specimens or in the normal prostate tissues (P
- Published
- 2011