Role of androgens in the growth of endometrial carcinoma: an in vivo animal model.
OBJECTIVE
We sought to create an animal model for the development of endometrial cancer in women with androgen excess. We examined the effects of estradiol and androgen, both alone and as precursors to estrogen biosynthesis on human endometrial cancers transplanted into a nude mouse model.


METHODS
We transplanted an estrogen-responsive, well-differentiated, established human endometrial carcinoma, EnCa-101, subcutaneously into athymic male nude mice. We established, first, that aromatase was expressed in this cell line, inducible by estrogen. We measured the growth of the tumor in the various groups weekly with Vernier calipers. We examined the effects of estradiol and androgens, both aromatizable and nonaromatizable, on tumor growth.


RESULTS
Estrogen-supplemented tumors showed the greatest rate of growth and were significantly greater than the growth rate in castrate mice. Androgen-supplemented tumors showed a growth rate similar to that of tumors without significant hormonal exposure (castrate mice). Dihydrotestosterone had no effect on tumor growth in comparison with an agonadal state.


CONCLUSIONS
Aromatizable and nonaromatizable androgens have little growth-promoting effect on a well-differentiated endometrial carcinoma. Estradiol is the most potent growth stimulus in our model.
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, 17033, USA.
R S
RS
Legro
A R
AR
Kunselman
S A
SA
Miller
P G
PG
Satyaswaroop
D000728:Androgens / Q000502:physiology*; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology*; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000473:pathology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology*; D009919:Orchiectomy; D012044:Regression Analysis; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000728:Androgens; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D013739:Testosterone; D004958:Estradiol; C013915:boldenone; D001141:Aromatase