Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content.
Prostate cancer is one of the most frequently diagnosed cancer in men. Treatment by radical prostatectomy, radiotherapy and anti-androgen drugs is successful in patients with localized cancer. However, prolonged androgen deprivation often leads to hormone refractory condition, associated with disease relapse. ErbB1 and ErbB2 activity has been correlated with androgen-independence. We determined the effects of GW2974, a dual inhibitor of ErbB-1 and ErbB-2 tyrosine kinase activity, on growth, NSE, chromogranin A and osteopontin cytosol content in the androgen-independent prostate cancer cell line PC-3. We found that PC-3 cell growth was inhibited by GW2974, whereas NSE and chromogranin A cell contents were stimulated and osteopontin cytosol level was not affected. The present data may have clinical implications for the treatment of advanced prostate cancer.
Terracciano
Daniela
D
Department of Cellular and Molecular Biology and Pathology L. Califano, University of Naples Federico II, I-80131 Naple, Italy.
Mazzarella
Claudia
C
Di Carlo
Angelina
A
Mariano
Angela
A
Ferro
Matteo
M
Di Lorenzo
Giuseppe
G
Giordano
Antonio
A
Altieri
Vincenzo
V
De Placido
Sabino
S
Macchia
Vincenzo
V
D000728:Androgens / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053379:Chromogranin A / Q000032:analysis / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D053379:Chromogranin A; D066246:ErbB Receptors; D053495:Osteopontin; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C506645:GW2974; C533270:NSMCE1 protein, human