Exon deletions and variants of human estrogen receptor mRNA in endometrial hyperplasia and adenocarcinoma.
Estrogen receptors (estrogen receptor alpha, ER) belong to a family of ligand-modulated transcription factors that play an important role in the progression of such tumors as breast and endometrial cancers. Functional domains, a set of mutations and variants produced by internal deletions of ER mRNA, have mainly been identified in breast cancer. Experimental results suggest that the presence of variants may result in different proteins which differ in activity and modulate the ER signaling pathway differently. We analyzed samples from 21 cases of endometrial hyperplasia and from 29 cases of endometrial cancer for the presence of internal exons and exon deletion variants of ER mRNA. ER and progesterone receptor (PgR) proteins were measured using Western blot technique in all endometrial cancer samples. We found that absence of the wild-type exon PCR product of ER mRNA in a sample increased in parallel with malignant potential in both sample types, whereas the number of exon deletion variants detected in the same sample decreased in cases of malignancy. The precise deletions of the respective exons suggest that they are probably the result of splicing errors. A relatively high number of variants in hyperplasia samples may indicate the important role of ER mRNA variants in the physiologic regulation of transcription in estrogen-sensitive genes. Eleven of 29 adenocarcinomas expressed a 62-kDa ER protein, truncated at the amino terminal, whereas all but one sample expressed a short 52 kDa variant ER protein. Our results suggest that differing ER proteins are generally present in human endometrial adenocarcinomas and that they may influence the estradiol signaling pathways.
Gynecologic Oncology Section, Research Laboratory, Department of Oncology, and Department of Gynecology and Obstetrics, Sahlgrenska University Hospital, Gothenburg, Sweden.
G.
G
Horvath
G.
G
Leser
M.
M
Hahlin
M.
M
Henriksson