Inhibition of rat mammary tumorigenesis by human chorionic gonadotropin associated with increased expression of inhibin.
This work was designed to test whether the suppression of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinomas by human chorionic gonadotropin (hCG) is associated with the synthesis of inhibin. For this purpose, virgin rats received 8 mg DMBA/100 g body weight; 20 d later they were injected daily with 100 IU of hCG for 40 d (DMBA+hCG group). Age-matched untreated (control), hCG-, and DMBA+saline-treated rats were used for comparisons. Mammary tissues were collected for histopathological and mRNA analyses after 5, 10, 20, and 40 d of hCG injection and 20 d after treatment. None of the animals in the control and hCG-treated groups developed mammary tumors. DMBA-treated rats developed a high incidence of both microscopic lesions, i.e., intraductal proliferations and ductal carcinomas in situ, and palpable tumors. In DMBA+hCG-treated rats, the incidence of microscopic and palpable tumors was markedly reduced. In these animals, alpha- and beta-inhibin immunoreactivity was elevated in the non-tumoral mammary glands in association with lobule formation and in the tumors. Inhibin A and B mRNAs were also elevated in the mammary tissue, and c-myc and c-jun were induced by the hormonal treatment. DMBA alone did not modify the expression of these genes. Our findings indicate that inhibin production and gene activation are associated with both mammary gland differentiation and tumor regression.
Srivastava
P
P
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Russo
J
J
Russo
I H
IH
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D007265:Inhibins / Q000096:biosynthesis* / Q000235:genetics; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
D002273:Carcinogens; D006063:Chorionic Gonadotropin; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D007265:Inhibins