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 ma mmary tumors (MTs) than in nonneoplastic breast tissue, IGF-II mRNA ab undance in DMBA-induced MTs is approximately 130-fold higher in pregna nt as compared to nonpregnant hosts, This correlated with accelerated tumor growth in pregnant hosts, Immunohistochemical studies of DMBA-in duced MTs with an anti-IGF-II antibody showed an intense staining of t umor 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 adjace nt normal breast tissue obtained during pregnancy. DMBA-induced MTs ex pressed high levels of type I receptor for IGFs as determined by North ern blots, In vitro studies confirmed that IGF-II is a mitogen for neo plastic 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 sug gest that this acceleration is mediated by up-regulation of IGF-II exp ression within neoplasms.