Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo.
The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959+/-0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G(1)/G(0) cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.
Abasolo
Ibane
I
Department of Urology, Northwestern University Medical School, Tarry 11-715, 303 E. Chicago Ave., Chicago, IL 60611, USA.
Yang
Luping
L
Haleem
Riffat
R
Xiao
Wuhan
W
Pio
Ruben
R
Cuttitta
Frank
F
Montuenga
Luis M
LM
Kozlowski
James M
JM
Calvo
Alfonso
A
Wang
Zhou
Z
D053607:Adrenomedullin; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014162:Transfection; D014183:Transplantation, Heterologous
D010455:Peptides; D053607:Adrenomedullin