[Profile of estrogen receptor alpha isoforms in endometrial adenocarcinoma].
Affectivity of activity of wild-type estrogen receptors forms depends not only from transcriptional activity of their encoding genes, but also from participation of ERs isoforms in entire ERs mRNA pool. Estrogen receptor mRNA isoforms are essential intracellular factor regulating cellular answer of estrogen. ERs expression, as well as the mRNA splice variants, may influence the biological properties of some tumors and affect their ability to respond to estrogen and antiestrogen therapies. The aim of the study was qualitative and quantitative analysis and comparison of mRNA ER-alpha and their isoforms concentration profile in endometrial adenocarcinoma and normal endometrium as control group. The level of ER-alpha mRNA was estimated using RT-QPCR method in proliferative phase (n = 12) and endometrial adenocarcinoma (n = 15). Types of alternative mRNA ER-alpha splice variants were marked. Seven transcripts ER-alpha (ER-alpha/delta 2, ER-alpha/3, ER-alpha/delta 2-3, ER-alpha 4-ER-alpha/delta 7) were quantitatively evaluated. Proportional analysis of particular mRNA ER-alpha isoforms participation in entire pool of mRNA ER-alpha showed diminution of ER-alpha/delta 2, ER-alpha/delta 2-3, ER-alpha/delta 7 what correlated with simultaneous decrease of mRNA copy number in endometrial adenocarcinoma. Endometrial adenocarcinoma was also characterized by presence of isoforms not stepping out in investigated segments of normal endometrium: ER-alpha/delta 4, ER-alpha/delta 6 and ER-alpha/delta 5 being with factor about high transcriptional activity potential, are able to activate transcription of estrogen receptors target genes independently from ligad binding. Additional ER-alpha isoforms appearing in endometrial adenocarcinoma instead of wild-type ER? proves, that in chance of tumor transformation the number of potranscriptional modifications increases. One can not exclude that their number is connected with genetic changes starting carcinogenesis in endometrium. Changes of mRNA ER-alpha copy number and presence of definite isoforms may altered of signaling estrogen pathways.
Witek
Andrzej
A
Katedry i Kliniki Połoznictwa i Ginekologii SAM w Katowicach.
Skałba
Piotr
P
Paul
Monika
M
Stojko
Rafał
R
Nawrocki
Michał
M
Mazurek
Urszula
U
Wilczok
Tadeusz
T
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000473:pathology; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D012326:RNA Splicing; D012334:RNA, Neoplasm / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen