In vivo effects of estrogens on c-erbB-2 oncoprotein levels in chorionic villous tissue and maternal serum.
The c-erbB-2-encoded oncoprotein p185 (HER2) is overexpressed in the fetal epithelium, the placenta and several carcinomas. Elevated serum levels of the released ectodomain (p105) were found in cancer patients and pregnant women at term. In cultured breast cancer cells estradiol inhibited p185 expression and induced growth arrest. These results prompted us to investigate the in vivo influence of serum estradiol and estriol on c-erbB-2 protein levels in pregnancy. We examined chorionic villous tissue extracts and maternal sera obtained from six legal abortions in the first trimester and 20 vaginal deliveries at term. For quantification of c-erbB-2 protein we employed an ELISA. In the first trimester maternal p105 serum levels were significantly (p < 0.0001) lower and p185 tissue levels significantly (p < 0.05) higher than in the third trimester. The highest p105 values were found in additionally examined cord blood. Interindividual regression analyses yielded inverse correlation between estradiol concentrations and placental p185 expression in the first (r = -0.58) and third trimester (r = -0.38) as well as p105 serum levels in the first trimester (r = -0.83). Estriol was correlated positively with p105 values in maternal and umbilical serum but not with placental p185 expression. We conclude that estradiol down-regulates p185 expression in pregnancy whereas the level of maternal p105 depends on the total amount of fetoplacental p185.
Mielke
S
S
Department of Obstetrics and Gynecology, University of Göttingen, Germany.
Meden
H
H
Marx
D
D
Wuttke
W
W
Kuhn
W
W
D002824:Chorionic Villi / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004964:Estriol / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000378:metabolism*; D012044:Regression Analysis
D004958:Estradiol; D004964:Estriol; D018719:Erb-b2 Receptor Tyrosine Kinases