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EGFR signaling pathway negatively regulates PSA expression and secretion via the PI3K-Akt pathway in LNCaP prostate cancer cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2006 Mar 31; Vol. 342 (1), pp. 92-100. Date of Electronic Publication: 2006 Feb 02. - Publication Year :
- 2006
-
Abstract
- Epidermal growth factor (EGF) and its receptor (EGFR) are involved in hormone-refractory growth and poor prognosis of a subgroup of human prostate cancer. In this communication, we investigated the regulation of PSA by the EGFR signaling pathway using LNCaP C-81 prostate cancer cells. Administration of EGF stimulated the growth of LNCaP C-81 cells, however, PSA expression and secretion were suppressed. An EGFR inhibitor, AG1478, abrogated the PSA suppression effect by EGF, in concurrence with the suppression of tyro-phosphorylation levels of EGFR. Interestingly, the AR level was also decreased in EGF-treated LNCaP C-81 cells. Moreover, LY294002, but not PD98059, inhibited the PSA and AR suppression effect by EGF in concurrence with the suppression of phosphorylation levels of Akt. In conclusion, our results strongly suggest the existence of a novel androgen-independent PSA regulatory mechanism, i.e., the EGFR signaling pathway negatively regulates PSA expression which may be induced by the alteration of AR expression via the PI3K-Akt pathway in LNCaP C-81 cells.
- Subjects :
- Androgens metabolism
Androgens pharmacology
Cell Line, Tumor
Chromones pharmacology
Down-Regulation
Epidermal Growth Factor metabolism
Epidermal Growth Factor pharmacology
ErbB Receptors antagonists & inhibitors
Gene Expression Regulation, Neoplastic drug effects
Humans
Immunohistochemistry
Male
Morpholines pharmacology
Neoplasm Staging
Organic Chemicals pharmacology
Prostatic Neoplasms pathology
Protein Kinase Inhibitors pharmacology
ErbB Receptors metabolism
Phosphatidylinositol 3-Kinases metabolism
Prostate-Specific Antigen metabolism
Prostatic Neoplasms metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 342
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 16472761
- Full Text :
- https://doi.org/10.1016/j.bbrc.2006.01.106