Transcriptional regulation of beta(1) integrin expression in the physio/pathological states of human endometrial tissues

beta(1C) integrin is a spliced variant of the human beta(1) integrin family that inhibits cell proliferation, at variance with beta(1A) that stimulates it. During the transition from normal to neoplastic endometrium, both variants are down-regulated at the mRNA level. but only beta(1C) at the protein level, suggesting a key role of the regulation of beta(1C) integrin expression in the pathogenesis of endometrial cancer. In this study we show for the first time that, besides beta(1A) and beta(1C), the beta(1B) 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 beta(1) integrin expression during endometrial cancer progression we compared the transcriptional activity of the beta(1) 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 beta(1) transcription rate that directly correlated with the increase in beta(1B), beta(1C) and beta(1A) steady-state mRNA levels. Finally, we compared the activity of the distal and proximal promoters of the beta(1) 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 beta(1) integrin variants during endometrial malignant transformation.