Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma.
OBJECTIVE
Activin A is a multifunctional growth and cell differentiation factor produced by normal endometrium, and secreted in high amounts by endometrial adenocarcinoma. In the present study we evaluated the expression of two inhibitory activin A ligands, follistatin and follistatin-related gene (FLRG), in endometrial adenocarcinoma and in age-matched healthy human endometrium.


METHODS
Atropic menopausal (n=13) and tumoral (n=9 adenocarcinoma) tissues were processed to evaluate mRNA expression levels (by semiquantitative RT-PCR) and peptide localization (by immunohistochemistry). Differences were evaluated by the unpaired t-test and assumed to be statistically significant when P<0.05.


RESULTS
Both control and tumoral endometrial samples express and localize follistatin and FLRG. However, whereas follistatin mRNA expression did not differ significantly, FLRG was significantly lower in endometrial adenocarcinoma than in healthy endometrial specimens (P<0.0001). With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity. Nuclear and cytoplasmic FLRG immunolocalization was seen in glands, and only nuclear immunolocalization was found in stroma and vessels of healthy endometrium. FLRG was weakly immunostained in endometrial adenocarcinoma.


CONCLUSIONS
Whilst follistatin expression is unchanged, FLRG is down-regulated in endometrial carcinoma. As activin A is a differentiation factor of human endometrium, the present findings support an imbalance between increased activin A and decreased FLRG expression in endometrial cancer, so that the failure of the activin A pathway through FLRG may be pivotal in endometrial tumorigenesis.
Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.
Pasquapina
P
Ciarmela
Pasquale
P
Florio
Matthildur
M
Sigurdardottir
Paolo
P
Toti
Veronique
V
Maguer-Satta
Ruth
R
Rimokh
Aldo
A
Altomare
Piero
P
Tosi
Felice
F
Petraglia
D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology*; D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D038681:Follistatin / Q000235:genetics* / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D012333:RNA, Messenger / Q000032:analysis
D038681:Follistatin; D038702:Follistatin-Related Proteins; D012333:RNA, Messenger