Induction of UO-44 Gene Expression by Tamoxifen in the Rat Uterus and Ovary*

Abstract

A complementary DNA, uterine-ovarian-specific gene 44 (UO-44), has been isolated from tamoxifen-induced rat uterine complementary DNA library using differential display techniques. UO-44 transcripts are found to be abundant in the uterus and ovary. UO-44 gene expression in the uterus is strictly regulated by estrogens, tamoxifen, and GH, whereas the pure antiestrogen ICI 182780 is inhibitory. Treatment of ovariectomized rats and hypophysectomized rats with tamoxifen and GH, respectively, resulted in up-regulation of UO-44 expression in a dose-dependent manner. In situ hybridization revealed that UO-44 gene expression was restricted to the luminal and glandular epithelial cells of the uterus and to granulosa cells of medium-size ovarian follicles. Transfection studies showed that UO-44 was a membrane-associated protein. Because estrogens, tamoxifen, and GH are stimulators of uterine luminal epithelial cell growth in vivo, UO-44 protein may serve as a mediator of the effect of these compounds in inducing epithelial proliferation and differentiation in these tissues.

Molecular cloning, characterization and isolation of novel spliced variants of the human ortholog of a rat estrogen-regulated membrane-associated protein, UO-44

“…The higher transcript levels of HuUO-44 in the metastatic tumor samples shown on the CPA (Figure 4), thus suggest that the HuUO-44 may promote tumor cell extravasation. The involvement of HuUO-44 in ovarian cancer cell attachment, metastasis and its induction by estrogens (Huynh et al, 2001), further highlights a potential role of HuUO-44 as a marker for early detection of the cancer or for hormone responsiveness in estrogen or antiestrogen treatment.…”

“…We have previously isolated a uterine and ovarian specific, tamoxifen and estrogen-induced rat UO-44 cDNA through differential display and cDNA library screening (Huynh et al, 2001). Our previous findings demonstrated that estrogen induces the expression of UO-44 while pure antiestrogen ICI 182780 is inhibitory.…”

“…The two CUB domains (CUB-1 and CUB-2) is indicated by and the ZP domain by . The signal peptide (SP) is indicated by ' at the amino terminal and a putative transmembrane region (TM) is indicated by at the carboxyl terminal Membrane-associated protein, CTC Leong et al previously demonstrated using in situ hybridization that UO-44 was restricted to the luminal and glandular epithelial cells in the rat (Huynh et al, 2001). In comparison, the rat multiple tissue expression profile is a better representation of the actual UO-44 expression as the rat Northern blot was generated using total RNA extracted from whole organs, compared to total RNA extracted from tissue sections used in the human MTN blot.…”

“…We previously reported a tamoxifen-induced complementary DNA (cDNA) RatUO-44 (GenBank Accession number AF022147) isolated from rat uterus cDNA library (Huynh et al, 2001). RatUO-44 is strictly regulated by estrogens, tamoxifen and growth hormone (GH), whereas pure antiestrogen ICI 182780 is inhibitory.…”

The anti-breast cancer drug tamoxifen alters Ca2+ movement in Chinese hamster ovary (CHO-K1) cells

“…Cysts and papillary serous carcinoma of the ovary has been noted in tamoxifentreated breast cancer patients (Kazandi et al 2002;Seoud et al 1999). In vitro, tamoxifen has been shown to induce UO-44 gene expression in the rat uterus and ovary (Huynh et al 2001), and to decrease the weight of rat ovary (D'Mello et al 1999). However, the mechanism underlying tamoxifen's effect on ovary is unclear.…”