Androgen deprivation therapy regulation of beta1C integrin expression in prostate cancer.
The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at variance with its wild-type counterpart, i.e., the beta1A 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 beta1C integrin during prostate malignant transformation. Here, we investigated whether androgen deprivation therapy (ADT) may affect beta1C mRNA expression in prostate cancer. Neoplastic prostates were obtained from patients undergoing radical prostatectomy who had received neoadjuvant ADT. The beta1C 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 beta1C integrin gene transcriptional activity was measured by nuclear Run-on assays. We found an increase of beta1C 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 beta1C integrin mRNA levels. Short-term administration of ADT seems to interfere with beta1C integrin expression, suggesting the existence of androgen-mediated pathways involving beta1C. 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.
Fuzio
Paolo
P
Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
Lucarelli
Giuseppe
G
Perlino
Elda
E
Battaglia
Michele
M
Bettocchi
Carlo
C
Selvaggi
Francesco Paolo
FP
Ditonno
Pasquale
P
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D015152:Blotting, Northern; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014105:Tosyl Compounds / Q000627:therapeutic use; D014158:Transcription, Genetic
D000726:Androgen Antagonists; D000813:Anilides; D019012:Integrin beta1; D009570:Nitriles; D012333:RNA, Messenger; D014105:Tosyl Compounds; C403487:integrin beta1C; D017273:Goserelin; C053541:bicalutamide