title: Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
abstract: METHODS
  Epidemiological studies provide evidence that consumption of cruciferous vegetables, like broccoli, can reduce the risk of cancer development. Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for this cancer-specific cytotoxicity remain unclear.
  
  
  RESULTS
  We utilized RNA sequencing and determined the transcriptomes of normal prostate epithelial cells, androgen-dependent prostate cancer cells, and androgen-independent prostate cancer cells treated with SFN. SFN treatment dynamically altered gene expression and resulted in distinct transcriptome profiles depending on prostate cell line. SFN also down-regulated the expression of genes that were up-regulated in prostate cancer cells. Network analysis of genes altered by SFN treatment revealed that the transcription factor Specificity protein 1 (Sp1) was present in an average of 90.5% of networks. Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells and Sp1 may be an important mediator of SFN-induced changes in expression.
  
  
  CONCLUSIONS
  Overall, the data show that SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA; Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Beaver
authors.forename: Alex
authors.initials: A
authors.lastname: Buchanan
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Sokolowski
authors.forename: Allison N
authors.initials: AN
authors.lastname: Riscoe
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Wong
authors.forename: Jeff H
authors.initials: JH
authors.lastname: Chang
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
mesh_terms: D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018890:Chemoprevention; D019587:Dietary Supplements / Q000009:adverse effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D017879:Isothiocyanates / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013454:Sulfoxides; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D013454:Sulfoxides; C016766:sulforaphane
keywords: Chemoprevention; Prostate cancer; RNA sequencing; Specificity protein 1; Sulforaphane