Estradiol inhibits growth of hormone-nonresponsive PC3 human prostate cancer cells.
Significant inhibition of proliferative activity in PC3 human prostate cancer cells by estradiol is reported, accompanied by experimental evidence for a specific estrogen receptor (ER). Radioligand-binding assays revealed the presence of high affinity sites of estrogen binding in the nuclear compartment of PC3 cells. In addition, using a reverse transcriptase-polymerase chain reaction system, we obtained evidence of either normal or a variant ER mRNA; the latter, which lacks the entire exon 4, is coexpressed with normal ER mRNA and has been recently characterized in our laboratories. The likelihood that the inhibitory effect exerted by estradiol could be mediated by an increase of transforming growth factor beta (TGF beta) production was also investigated. Use of monoclonal antibodies against TGF beta 1 produced a 3-fold increase of growth rate in PC3 cells; this clearly speaks for high levels of endogenous TGF beta 1. This effect was almost completely abolished after addition of 100 nM estradiol. However, we failed to demonstrate any increase of TGF beta 1 mRNA after estradiol administration using Northern blot analysis. Further studies are needed to ascertain whether the estradiol-induced growth inhibition of PC3 cells is either mediated by other TGF beta species or exerted via alternative mechanism(s).
Carruba
G
G
Hormone Biochemistry Laboratories, Medical School, University of Palermo, Italy.
Pfeffer
U
U
Fecarotta
E
E
Coviello
D A
DA
D'Amato
E
E
Lo Castro
M
M
Vidali
G
G
Castagnetta
L
L
D015152:Blotting, Northern; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D004958:Estradiol