Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in the rat uterus.

A human estrogen regulated transcript, HEM45, was characterized that encodes a novel protein of 181 amino-acid residues (Mr 20300). It was identified using differential-display-PCR and mRNA from a human cervical cancer cell line (UP1) stably transfected with an estrogen receptor (ER) expression construct. The HEM45 protein has similarity to the bracket fungus protein FRT1 that can cause fruiting-body production and to a Xenopus product, XPMC2, that affects cell-cycle control. These similarities suggest that HEM45 will have a role in mediating estrogen control of cellular proliferation and differentiation. HEM45 mRNA was widely expressed at low levels in cell lines and was up regulated by E2 in ER-positive breast cancer lines. The in vivo regulation of HEM45 was confirmed by demonstrating estrogen stimulation of the rat HEM45 homolog in the rat uterus. The levels of the rat uterine HEM45 sequence were elevated by estrogen 3 to 15 h after treatment. The maximal response, at six hours, was greater than eight-fold. The uterine HEM45 response was distinct from that reported for 'early-response' genes as the 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 direct ER-regulation of HEM45.