Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta-estradiol.
OBJECTIVE
Estrogen treatment has long been known to be of benefit in prostate cancer (CaP), but its mechanism was thought to involve merely a reduction in androgen levels. However, new evidence indicates that estrogen may exert effects on CaP cells in the absence of androgens.


METHODS
Implantation of CaP xenografts (LuCaP 35, LuCaP 49, LuCaP 58, LuCaP 73, PC-3, and LNCaP) into intact and ovariectomized female mice was done to characterize growth and take rates in the absence of androgens. Ovariectomized female mice were supplemented with 17beta-estradiol, and LuCaP 35 CaP xenograft take and growth rates were determined. Reverse transcription-PCR was used to evaluate the presence of the estrogen receptor messages in CaP xenografts.


RESULTS
We have observed significant inhibition of CaP growth in intact versus ovariectomized female animals in five of six CaP xenograft lines. 17beta-Estradiol supplements given to ovariectomized female mice led to inhibition of tumor establishment and diminished growth of LuCaP 35 similar to that observed in intact female mice. Using reverse transcription-PCR, we have shown that these xenografts express the estrogen receptor beta message.


CONCLUSIONS
We have determined that 17beta-estradiol supplementation causes inhibition of CaP growth in an animal model by mechanisms that are independent of androgen action. This gives rise to the possibility that estrogen therapy may be of potential use with hormone-refractory cancers. The xenograft models we describe herein may be useful as well in elucidating the pathways mediating the androgen-independent effects of estrogen on CaP.
Corey
Eva
E
Department of Urology, University of Washington, Seattle, Washington 98195, USA. ecorey@u.washington.edu
Quinn
Janna E
JE
Emond
Mary J
MJ
Buhler
Kent R
KR
Brown
Lisha G
LG
Vessella
Robert L
RL
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D047629:Estrogen Receptor beta; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010052:Ovariectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D047629:Estrogen Receptor beta; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D004958:Estradiol