Hormonal regulation of H19 gene expression in prostate epithelial cells.
The H19 gene is transcribed in an mRNA-like noncoding RNA. When tumors of various organs or cell types are considered, H19 oncogene or tumor-suppressor status remains controversial. To address the potential regulation of H19 gene expression by an androgen steroid hormone (DHT: dihydrotestosterone) or by a peptidic hormone (PRL: prolactin), we performed experiments in rats systemically treated with chemical mediators. This range of in vivo experiments demonstrated that chronic hyperprolactinemia upregulated the H19 expression in epithelial and stromal cells whereas DHT downregulated the gene. PRL and DHT appeared to be opposite mediators in the H19 RNA synthesis. We investigated these hormonal effects in three human prostate epithelial cell lines. In LNCaP cancer cells, the opposite effect of PRL and DHT was corroborated. However, in normal cells (PNT1A), H19 remained insensitive to the hormones in fetal calf serum (FCS) medium but became responsive in a serum-stripped medium. In the DU-145 cancer cell line, tested for its androgen-independence and aggressiveness, the hormones had no effect on H19 expression whatever the culture conditions. Finally, we demonstrated that PRL upregulated the H19 expression in LNCaP cells by the JAK2-STAT5 transduction pathway. We conclude that H19 expression is regulated by both a peptidic and a male steroid hormone.
Berteaux
N
N
Unité INSERM ESPRI: Signalisation des facteurs de croissance dans le cancer du sein, Protéomique fonctionnelle, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Lottin
S
S
Adriaenssens
E
E
Van Coppenolle
F
F
Van Coppennolle
F
F
Leroy
X
X
Coll
J
J
Dugimont
T
T
Curgy
J-J
JJ
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D053614:Janus Kinase 2; D008297:Male; D008894:Milk Proteins / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D051381:Rats; D017208:Rats, Wistar; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D013196:Dihydrotestosterone; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2