Effects of estradiol on the expression and production of IGFBP-2 by R3230AC mammary tumor cells.

Overview

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 have been recently identified in this tumor in vivo and in vitro. Using western blotting techniques on tumor tissue homogenates or conditioned media, we demonstrated that IGFBP-2 and, to a lesser extent, IGFBP-3 were expressed, produced, and secreted by the R3230AC tumor cells. Moreover, immunohistochemical assessment of tumor sections with anti-IGFBP-2 demonstrated that signal for IGFBP-2 was localized in the neoplastic glandular epithelium and often in the lumina of the pseudoglandular structures characteristic of this neoplasm. Expression of IGFBP-2 is regulated by the estrogen status of the host. The significant increase occurring in tumors from ovariectomized hosts was completely reversed 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 culture medium. Thus, the response of IGFBP-2 to estrogen showed agreement both in vivo and in vitro, whereas progesterone had no significant effect on these parameters. In the R3230AC tumor, estrogen treatment in vivo decreases tumor growth. Therefore, a relationship could exist between the action of estradiol to inhibit production of IGFBP-2 and the ability of estrogens to regulate tumor growth.