Expression of E-cadherin transcriptional regulators in ovarian carcinoma.
Unlike most epithelial cancers, E-cadherin expression is upregulated in ovarian carcinoma effusions compared with corresponding primary tumors. In the present study, we analyzed the anatomic site-specific expression of transcription factors that negatively regulate E-cadherin in ovarian carcinoma. Using reverse-transcription polymerase chain reaction, mRNA in situ hybridization, and Western blotting, we analyzed the expression and localization of the Snail, Slug, and SIP1 transcription factors and E-cadherin in 78 effusions, 41 primary carcinomas, and 15 solid metastases. Slug mRNA and protein expression was highest in metastases (p=0.042 and p<0.001, respectively). Snail mRNA was comparable at all anatomic sites, but higher protein expression was found in primary tumors and solid metastases compared with effusions (p<0.001). SIP1 mRNA expression was higher in effusions (p<0.001) compared to other sites. Confocal microscopy analysis of fresh and cultured cells from effusion specimens revealed cytoplasmic localization of the Snail protein in primary tumor cells, with a nuclear shift following culturing of these cells. In conclusion, E-cadherin and its negative regulators show site-dependent expression in ovarian carcinoma. In solid tumors, E-cadherin is negatively regulated by Snail and Slug. In effusions, SIP1 may be the main regulator of E-cadherin, but with a lesser level of suppression compared with primary tumors and solid metastases.
Elloul
Sivan
S
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Silins
Ilvars
I
Tropé
Claes G
CG
Benshushan
Avi
A
Davidson
Ben
B
Reich
Reuven
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015820:Cadherins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
D015820:Cadherins; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors