Document Detail


Secretory phospholipase A2-IIa is involved in prostate cancer progression and may potentially serve as a biomarker for prostate cancer.
MedLine Citation:
PMID:  20837598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The majority of prostate cancers are indolent, whereas a significant portion of patients will require systemic treatment during the course of their disease. To date, only high Gleason scores are best associated with a poor prognosis in prostate cancer. No validated serum biomarker has been identified with prognostic power. Previous studies showed that secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in almost all human prostate cancer specimens and its elevated levels are correlated with high tumor grade. Here, we found that sPLA2-IIa is overexpressed in androgen-independent prostate cancer LNCaP-AI cells relative to their androgen-dependent LNCaP cell counterparts. LNCaP-AI cells also secrete significantly higher levels of sPLA2-IIa. Blocking sPLA2-IIa function compromises androgen-independent cell growth. Inhibition of the ligand-induced signaling output of the HER network, by blocking PI3K-Akt signaling and the nuclear factor-kappaB (NF-κB)-mediated pathway, compromises both sPLA2-IIa protein expression and secretion, as a result of downregulation of sPLA2-IIa promoter activity. More importantly, we demonstrated elevated serum sPLA2-IIa levels in prostate cancer patients. High serum sPLA2-IIa levels are associated significantly with high Gleason score and advanced disease stage. Increased sPLA2-IIa expression was confirmed in prostate cancer cells, but not in normal epithelium and stroma by immunohistochemistry analysis. We showed that elevated signaling of the HER/HER2-PI3K-Akt-NF-κB pathway contributes to sPLA2-IIa overexpression and secretion by prostate cancer cells. Given that sPLA2-IIa overexpression is associated with prostate development and progression, serum sPLA2-IIa may serve as a prognostic biomarker for prostate cancer and a potential surrogate prostate biomarker indicative of tumor burden.
Authors:
Zhongyun Dong; Yin Liu; Kieran F Scott; Linda Levin; Krishnanath Gaitonde; R Bruce Bracken; Barbara Burke; Qihui Jim Zhai; Jiang Wang; Leslie Oleksowicz; Shan Lu
Related Documents :
17263128 - Targeting metastatic prostate cancer: the search for innovative systemic therapies.
7500468 - Familial aspects of prostate cancer: a case control study.
16322328 - Compartmentalized expression of kallikrein 4 (klk4/hk4) isoforms in prostate cancer: nu...
17153888 - Repeated massive tongue swelling due to the combined use of estramustine phosphate and ...
19673018 - No association between phosphatase and tensin homolog genetic polymorphisms and colon c...
17263128 - Targeting metastatic prostate cancer: the search for innovative systemic therapies.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-13
Journal Detail:
Title:  Carcinogenesis     Volume:  31     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-11-16     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1948-55     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Cincinnati College of Medicine, 2120 East Galbraith Road, Cincinnati, OH 45237-0507, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Proliferation
Cells, Cultured
Disease Progression
Enzyme-Linked Immunosorbent Assay
Group II Phospholipases A2 / physiology*
Humans
Male
NF-kappa B / metabolism
Neoplasm Staging
Neoplasms, Hormone-Dependent / blood,  genetics,  pathology*
Phosphatidylinositol 3-Kinases / metabolism
Prostatic Neoplasms / blood,  genetics,  pathology*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Messenger / genetics
RNA, Small Interfering / pharmacology
Receptor, erbB-2 / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tumor Markers, Biological / blood*
Grant Support
ID/Acronym/Agency:
CA131137/CA/NCI NIH HHS; R01 CA119935/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Tumor Markers, Biological; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.1.4/Group II Phospholipases A2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dietary nucleotides and early growth in formula-fed infants: a randomized controlled trial.
Next Document:  EpCAM in carcinogenesis: the good, the bad or the ugly.