Carcinogenesis, Vol 18, 1799-1808, Copyright © 1997 by Oxford University Press
P Srivastava, J Russo and IH Russo
Human chorionic gonadotropin (hCG) inhibits the progression of 7,12-
dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to
determine whether this phenomenon was mediated by induction of programmed
cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8
mg DMBA/100 g body weight; 20 days later they were injected daily with 100
IU hCG for 40 days (DMBA + hCG group). Age- matched untreated, hCG- and
DMBA + saline treated rats were used as controls. Tissues were collected at
the time of DMBA administration and at 5, 10, 20 and 40 days of hCG
injection. RNA from mammary glands, adenocarcinomas and ovaries was probed
for transforming growth factors (TGF) alpha and beta, and the apoptotic
genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands
of hCG-treated animals with or without DMBA exhibited elevated expression
of TRPM2, ICE, bcl-XS, c- myc and p53; and elevation in the apoptotic
index. Mammary adenocarcinomas developed in those animals treated with hCG
showed an elevation in the expression of p53, c-myc and ICE genes in
comparison with the levels detected in the adenocarcinomas developed by the
animals treated with DMBA alone. No significant alterations in the
expression of any of the genes tested was observed in ovarian RNAs. These
results led us to conclude that hCG induces programmed cell death in the
mammary gland initiated in the carcinogenic process, that this process is
p53 dependent, and is modulated by c-myc expression. Our data also indicate
the possibility that a cell death program dependent on the bcl2 family
exists, because of the potential involvement of p53, bcl-XS and Bax in
apoptosis. This additional mechanism of tumor inhibition makes hCG
treatment a useful approach for the prevention and therapy of breast
cancer.
ARTICLES
Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
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