title: Androgen deprivation therapy affects BCL-2 expression in human prostate cancer.
abstract: BCL-2 is an integral protein of the external mitochondrial membrane that inhibits cell apoptotic death. We investigated the effect of androgen deprivation therapy (ADT) on BCL-2 expression in prostate cancer tissues. We studied BCL-2 expression in vivo in prostate cancer tissues obtained from patients who underwent radical prostatectomy after neoadjuvant ADT, by Northern and Western blot analysis, and immunohistochemistry. Moreover, gene transcriptional activity was also measured by nuclear run-on experiments. We demonstrated an increase of BCL-2 mRNA expression in patients who underwent neoadjuvant ADT for 1 month in comparison to patients who had not received any therapy. Moreover, we demonstrated that there were no significant modifications of BCL-2 mRNA levels in patients who underwent neoadjuvant ADT for 3 and 6 months. Furthermore, BCL-2 protein levels in patients who underwent neoadjuvant ADT for 1 month were upregulated in comparison to patients who had not received any therapy. Immunohistochemical analysis showed a strong positivity of prostate cells depending on ADT administration for 1 month. Finally, transcriptional activity was not modified in patients who underwent neoadjuvant ADT, suggesting the absence of hormonal regulation on BCL-2 gene expression at the transcriptional level. Our data show that short-term administration of ADT interferes with BCL-2 expression, suggesting that androgen-mediated mechanisms may act through BCL-2-mediated apoptotic pathways. Moreover, since short-term ADT administration does not interfere with BCL-2 expression at the transcriptional level, the androgen-mediated mechanisms involving BCL-2 pathways, probably act at the post-transcriptional level.
authors.affiliation: Institute for Biomedical Technologies, ITB-CNR - Via G. Amendola, 122/D, 70126 Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fuzio
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Carlo
authors.initials: C
authors.lastname: Bettocchi
authors.forename: Trabucco
authors.initials: T
authors.lastname: Senia
authors.forename: Elda
authors.initials: E
authors.lastname: Perlino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger