Androgen Deprivation Therapy Regulation of Beta1C Integrin Expression in ProstateCancer

The ?1C integrin is an alternatively spliced variant of the ?1 integrin subfamily that at variance with its wild-type counterpart, i.e., the ?1A integrin, inhibits cell proliferation in prostate cancer cells. We have recently shown that transcriptional, translational and post-translational processes contribute to the selective loss of ?1C integrin during prostate malignant transformation. Here, we investigated whether androgen deprivation therapy (ADT) may affect ?1C mRNA expression in prostate cancer. Neoplastic prostates were obtained from patients undergoing radical prostatectomy who had received neoadjuvant ADT. The ?1C mRNA level was measured by Northern hybridization experiments and compared to normal prostates obtained from patients who underwent radical cystoprostatectomy for bladder cancer. Furthermore, the ?1C integrin gene transcriptional activity was measured by nuclear Run-on assays. We found an increase of ?1C mRNA expression (208±11%; p<0.01) in patients who received ADT in comparison to those who did not. Furthermore, we demonstrated an increase of gene transcriptional activity (360±10%; p<0.01) possibly partially or completely responsible for the regulation of the ?1C integrin mRNA levels. Short-term administration of ADT seems to interfere with ?1C integrin expression, suggesting the existence of androgen-mediated pathways involving ?1C. Precise characterization of the mechanisms that regulate the expression of this factor in cancer cells will provide further insight into the molecular mechanisms involved in tumor progression and possibly contribute to the identification of molecular targets for the development of new therapeutic strategies.