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Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer.

Sarwar, Martuza LU ; Sandberg, Sabina LU ; Abrahamsson, Per-Anders LU and Persson, Jenny L LU (2014) In Urologic Oncology 32(1).
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... (More)
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<0.01) and was reversely correlated with AR expression. Conversely, AR and PRKAR2B mRNA expressions were significantly higher in metastatic lesions than those in the primary CaP specimens or in the normal prostate tissues (P<0.01). CONCLUSION: Our study revealed a novel mechanism to precisely define the functional and clinical interrelationship between the cAMP/PKA pathway and AR signaling in the development of androgen-independent growth of CaPs and metastasis progression. (Less)
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organization
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type
Contribution to journal
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published
subject
in
Urologic Oncology
volume
32
issue
1
publisher
Elsevier
external identifiers
  • pmid:23410945
  • wos:000347243300008
  • scopus:84890794538
ISSN
1873-2496
DOI
10.1016/j.urolonc.2012.08.019
language
English
LU publication?
yes
id
13bad505-4c57-45dc-9551-3b42827dc771 (old id 3559767)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23410945?dopt=Abstract
date added to LUP
2013-03-04 13:07:46
date last changed
2017-08-06 03:14:12
@article{13bad505-4c57-45dc-9551-3b42827dc771,
  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&lt;0.01) and was reversely correlated with AR expression. Conversely, AR and PRKAR2B mRNA expressions were significantly higher in metastatic lesions than those in the primary CaP specimens or in the normal prostate tissues (P&lt;0.01). CONCLUSION: Our study revealed a novel mechanism to precisely define the functional and clinical interrelationship between the cAMP/PKA pathway and AR signaling in the development of androgen-independent growth of CaPs and metastasis progression.},
  author       = {Sarwar, Martuza and Sandberg, Sabina and Abrahamsson, Per-Anders and Persson, Jenny L},
  issn         = {1873-2496},
  language     = {eng},
  number       = {1},
  publisher    = {Elsevier},
  series       = {Urologic Oncology},
  title        = {Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer.},
  url          = {http://dx.doi.org/10.1016/j.urolonc.2012.08.019},
  volume       = {32},
  year         = {2014},
}