The human prolactin receptor gene structure and alternative promoter utilization: The generic promoter hPIII and a novel human promoter hP(N)

The 5'-untranslated region of the human prolactin receptor (hPRLR) gene con tains two alternative first exons, hE1(3), the human counterpart of the rat and mouse E1(3) and a novel human type of alternative first exon termed hE 1(N), also a common non-coding exon 2 and a third exon containing the trans lation initiation codon. hE1(3) was localized similar to 800 bp 5' from the hE1(N) in the genome. The two distinct first exons hE1(3) and hE1(N) are e xpressed in human breast tissue, breast cancer cells, gonads and liver. Ove rall, the transcript containing hE1(3) is prevalent in most tissues. The co ding region of the gene comprises eight exons (exon 3-10), in which exon 10 encodes most of the intracellular domain. hE1(3) and hE1(N) are transcribe d from alternative promoters hPIII and hP(N), respectively. The hPIII, cont aining identical Sp1 and C/EBP elements as in the rodent promoters, shares 81% similarity in the region -480/-106 to both the rat and mouse. The novel promoter hP(N) contains putative binding sites for ETS-family proteins and a half-site for nuclear receptors. Therefore, both promoters likely utiliz e distinct mechanisms in controlling the hPRLR gene transcription. The diff erent promoter utilization of the hPRLR gene in diverse tissues may confer differential prolactin response through activation of different promoters.