EXPRESSION AND ESTROGEN REGULATION OF THE HEM45 MESSENGER-RNA IN HUMAN TUMOR LINES AND IN THE RAT UTERUS

A human estrogen regulated transcript, HEM45, was characterized that e ncodes a novel protein of 181 amino-acid residues (M-r 20300). It was identified using differential-display-PCR and mRNA from a human cervic al cancer cell Line (UP1) stably transfected with an estrogen receptor (ER) expression construct. The HEM45 protein has similarity to the br acket fungus protein FRT1 that can cause fruiting-body production and to a Xenopus product, XPMC2, that affects cell-cycle control. These si milarities suggest that HEM45 will have a role in mediating estrogen c ontrol of cellular proliferation and differentiation. HEM45 mRNA was w idely expressed at low levels in cell Lines and was up regulated by E- 2 in ER-positive breast cancer lines. The in vivo regulation of HEM45 was confirmed by demonstrating estrogen stimulation of the rat HEM45 h omolog in the rat uterus. The levels of the rat uterine HEM45 sequence were elevated by estrogen 3 to 15 h after treatment. The maximal resp onse, at six hours, was greater than eight-fold. The uterine HEM45 res ponse was distinct from that reported for 'early-response' genes as th e increase in HEM45 mRNA levels occurred later but could be induced by lower levels of hormone. HEM45 mRNA expression in cultured cells was increased by estrogen in the presence of cycloheximide, indicating dir ect ER-regulation of HEM45. (C) 1998 Elsevier Science Ltd. All rights reserved.