Transcriptional regulation of the beta1C integrin splice variant in human prostate adenocarcinoma.
Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behaviour, including motility and invasiveness, cell growth and cell survival. beta1C integrin, an alternatively spliced variant of the human beta1 integrin, has been shown to inhibit cell proliferation. We have previously demonstrated that beta1C integrin mRNA and protein are present in normal prostate and are down-regulated in prostate adenocarcinoma. To explore some of the molecular mechanisms regulating beta1C integrin gene expression, we have analysed the transcriptional activity of the beta1 integrin gene in neoplastic and normal human prostate tissue. Run-on analysis demonstrates that the transcription rate of the beta1 integrin gene is significantly reduced in prostate cancer specimens compared to normal prostate, thus accounting for the reduction in mRNA levels of the beta1 integrin variants. Moreover, the decrease in transcriptional activity of the beta1 integrin gene directly correlates to the reduction of beta1C integrin steady-state mRNA levels (r=0.78).
Moro
Loredana
L
Institute of Biomembranes and Bioenergetics, C.N.R., 70126 Bari, Italy.
Greco
Margherita
M
Ditonno
Pasquale
P
Battaglia
Michele
M
Marra
Ersilia
E
Perlino
Elda
E
D000368:Aged; D017398:Alternative Splicing; D015152:Blotting, Northern; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D019012:Integrin beta1; D012333:RNA, Messenger; C403487:integrin beta1C; D012313:RNA