Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer.
The potent vasoconstrictor endothelin-1 (ET-1) is at its highest concentration in the normal human ejaculate and is associated with the progression of metastatic prostate cancer. ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. The ETA-selective receptor antagonist A-127722 inhibits ET-1-stimulated growth, but the ETB-selective receptor antagonist BQ-788 does not. ET-3, an ETB-selective agonist, also had no effect on prostate cancer growth. No specific ETB-binding sites could be demonstrated in any established human prostate cancer cell line tested, and ETB mRNA, detected by reverse transcription PCR, was reduced. The predominance of ETB binding on human benign prostatic epithelial tissue is not present in metastatic prostate cancer by autoradiography. In human prostate cancer progression to metastases, ET-1 and ETA expression are retained, whereas ETB receptor expression is reduced.
Nelson
J B
JB
James Buchanan Brady Urological Institute Research Laboratories, Johns Hopkins Hospital, Baltimore, Maryland 21287-2411, USA.
Chan-Tack
K
K
Hedican
S P
SP
Magnuson
S R
SR
Opgenorth
T J
TJ
Bova
G S
GS
Simons
J W
JW
D017209:Apoptosis / Q000187:drug effects; D000077868:Atrasentan; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000096:biosynthesis* / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008297:Male; D008940:Mitotic Index; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000378:metabolism; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D017931:DNA Primers; D004273:DNA, Neoplasm; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D011759:Pyrrolidines; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000077868:Atrasentan