| Research Abstract |
The aim of the research project is to investigate the regulatory mechanism of expression of estrogen receptors in the human normal uterine endometrium and endometrial cancer tissues. To do this, we have analyzed the structure of the cDNAs for the estrogen receptor alpha (Erα), estrogen receptor beta (ERP) and progesterone receptor (PR) of the human by the cDNA cloning method. The testicular cDNA library was screened by the hormone binding domaincorresponding CDNA fragments of the Era, Erp and PR. The novel cDNA isoforms of the Erα (Erα isoform S cDNA), Erβ (Erβ isoform M cDNA) and PR・(PR isoform S cDNA and PR isoform T cDNA) have been cloned. These cDNA isoforms contained the previously unidentified 5'-sequences on the exons 4-8 (Erα isoform S CDNA), the exons 5-8 (Erβ isoform M cDNA) or the exons 4-8 (PR isoforms S cDNA and PR isoform T cDNA). We further carried out the genomic DNA Analysis, indicating that the 5' -sequensces were derived from the novel independent exons, the Erα exon S, Erβ exon M, PR exon S and pr exon T, respectively. Although the genomic location of the Erα exon S is uclear, it is indicated that the Erβ exon M is located between the exon 4 and exon 5, and that the PR exon S and PR exon T are located in the upstream region of the exon 1. Moreover, the existence of these mRNA isoforms in the normal uterine endometrium and endometrial cancer tissues was analyzed by the RT-PCR. Low but definite levels of these mRNA isoforms were detected, indicating that these cDNA isoforms were not the cloning artifacts. From these results, we conclude that (1) the gene for the female sex steroid hormone receptors contain the novel intronic exons, (2) the novel mRNA isoforms are transcribed using the intronic exon and the exons 4-8 (or exons 5-8) of the gene, and (3) the isoform receptor proteins, possibly expressed in the normal uterine endometrium and endometrial cancer tissues, might play some physiological and/or pathological roles in these tissues.
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