Pregnancy-dependent growth of mammary tumors is associated with overexpression of insulin-like growth factor II.
We demonstrate that although IGF-II gene expression is approximately 3-fold higher in 9,10-dimethyl-1,2-benzanthracine (DMBA)-induced rat mammary tumors (MTs) than in nonneoplastic breast tissue, IGF-II mRNA abundance in DMBA-induced MTs is approximately 130-fold higher in pregnant as compared to nonpregnant hosts. This correlated with accelerated tumor growth in pregnant hosts. Immunohistochemical studies of DMBA-induced MTs with an anti-IGF-II antibody showed an intense staining of tumor cells for IGF-II, whereas a very low staining signal was observed for normal epithelial cells in the lobules. A similar immunostaining pattern was observed in three of three human ductal cancers and adjacent normal breast tissue obtained during pregnancy. DMBA-induced MTs expressed high levels of type I receptor for IGFs as determined by Northern blots. In vitro studies confirmed that IGF-II is a mitogen for neoplastic epithelial cells derived from DMBA-induced MTs. These results demonstrate that hormonal changes associated with pregnancy accelerate breast cancer cell proliferation in the DMBA-induced MT model and suggest that this acceleration is mediated by up-regulation of IGF-II expression within neoplasms.
Huynh
H
H
Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Alpert
L
L
Pollak
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002455:Cell Division; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D007335:Insulin-Like Growth Factor II