Transcriptional regulation of beta1 integrin expression in the physio/pathological states of human endometrial tissues.
beta1C integrin is a spliced variant of the human beta1 integrin family that inhibits cell proliferation, at variance with beta1A that stimulates it. During the transition from normal to neoplastic endometrium, both variants are down-regulated at the mRNA level, but only beta1C at the protein level, suggesting a key role of the regulation of beta1C integrin expression in the pathogenesis of endometrial cancer. In this study we show for the first time that, besides beta1A and beta1C, the beta1B spliced variant is expressed in human endometrium, and is up-regulated in hyperplastic and neoplastic endometria in comparison with normal proliferative endometria. To investigate the mechanisms of regulation of beta1 integrin expression during endometrial cancer progression we compared the transcriptional activity of the beta1 integrin gene in normal and diseased endometria by nuclear run-on analysis and we found it significantly reduced in endometrial adenocarcinoma. On the contrary, hyperplastic endometria showed a 2-fold increase in the beta1 transcription rate that directly correlated with the increase in beta1B, beta1C and beta1A steady-state mRNA levels. Finally, we compared the activity of the distal and proximal promoters of the beta1 gene integrin gene in normal and diseased endometria and we found the activity of the proximal promoter decreased in neoplastic endometria and increased in hyperplastic tissues, whereas the activity of the distal promoter did not change in different endometrial physio/pathological conditions. These findings suggest a complex pattern for regulation of the expression of beta1 integrin variants during endometrial malignant transformation.
Moro
Loredana
L
Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy.
Greco
Margherita
M
Maiorano
Eugenio
E
Selvaggi
Luigi
L
Marra
Ersilia
E
Perlino
Elda
E
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
D019012:Integrin beta1; D012333:RNA, Messenger; D012313:RNA