EFFECTS OF ESTRADIOL ON THE EXPRESSION AND PRODUCTION OF IGFBP-2 BY R3230AC MAMMARY-TUMOR CELLS

The R3230AC mammary adenocarcinoma of the Fischer rat possesses Type I and Type II IGF receptors. The mRNAs for IGFBP-2, -3, -4, -5 and -6 h ave been recently identified in this tumor in vivo and in vitro. Using western blotting techniques on tumor tissue homogenates or conditione d media, we demonstrated that IGFBP-2 and, to a lesser extent, IGFBP-3 were expressed, produced, and secreted by the R3230AC tumor cells. Mo reover, immunohistochemical assessment of tumor sections with anti-IGF BP-2 demonstrated that signal for IGFBP-2 was localized in the neoplas tic glandular epithelium and often in the lumina of the pseudoglandula r structures characteristic of this neoplasm. Expression of IGFBP-2 is regulated by the estrogen status of the host. The significant increas e occurring in tumors from ovariectomized hosts was completely reverse d with hormone repletion. Both mRNA expression and production of IGFBP -2 in vitro were also regulatable by the presence of estradiol-17 beta , with both processes being inhibited by its addition to the cell cult ure medium. Thus, the response of IGFBP-2 to estrogen showed agreement both in vivo and in vitro, whereas progesterone had no significant ef fect on these parameters. In the R3230AC tumor, estrogen treatment in vivo decreases tumor growth. Therefore, a relationship could exist bet ween the action of estradiol to inhibit production of IGFBP-2 and the ability of estrogens to regulate tumor growth. Copyright (C) 1996 Else vier Science Inc.