Estrogen receptor alpha mRNA variant lacking exon 5 is co-expressed with the wild-type in endometrial adenocarcinoma.
BACKGROUND
Endometrial adenocarcinoma is a typical estrogen-dependent neoplasia. The molecular mechanisms underlying carcinogenesis in the endometrium are still largely unknown. Recently, estrogen receptor (ER) mRNA splicing variants have been investigated in several normal and neoplastic human tissues. It has been suggested that the variant receptors compete with the wild-type receptors and thereby modulate the effects of estrogens and related steroids.


OBJECTIVE
To investigate the possible expression of the ER alpha mRNA variant-type lacking exon 5 (ERDelta5) in endometrial adenocarcinoma and peritumoral tissues, non-neoplastic endometrium of healthy women served as control.


METHODS
The study included 16 patients divided in two groups. The first group (n=6) was submitted to hysteroscopy and endometrial biopsy for metrorrhage, showing normal proliferative (n=2) or secretory (n=4) endometrium, the second group (n=10) included patients submitted to hysterectomy for endometrial adenocarcinoma (stages Ib-IIIb). In this latter group, specimens from peritumoral tissues were also analyzed (n=3). Characterization of the variant and wild-type alpha estrogen receptor transcripts was performed by RT-PCR with primers located in exons 4 and 6, followed by southern hybridization with probes directed to a specific 29 nucleotide sequence of exon 6, internal to the amplified fragments.


RESULTS
The ER alpha mRNA variant was co-expressed with the wild-type ER in five or six samples of non-neoplastic endometrium and in 10/10 cases of adenocarcinoma, with a more intense hybridization signal corresponding to the wild-type 439bp band compared to the variant-type 300bp band. Specimens from peritumoral tissue also expressed the variant ERDelta5 along with wild-type ER.


CONCLUSIONS
The presence of alpha mRNA variant lacking exon 5 in both normal and endometrial adenocarcinoma do not support a major role of variant estrogens receptors in the biology of endometrial cancer.
Cobellis
Luigi
L
Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.
Reis
Fernando M
FM
Driul
Lorenza
L
Vultaggio
Giuseppe
G
Ferretti
Ilva
I
Villa
Erica
E
Petraglia
Felice
F
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001706:Biopsy; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004717:Endometrium / Q000737:chemistry / Q000473:pathology; D047628:Estrogen Receptor alpha; D005091:Exons; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D015907:Hysteroscopy; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen