15-lipoxygenase 2 (15-LOX2) is a functional tumor suppressor that regulates human prostate epithelial cell differentiation, senescence, and growth (size).
15-Lipoxygenase 2 (15-LOX2) is the major mammalian lipoxygenase expressed in normal human adult prostate and its expression is decreased or lost in high-grade prostate intraepithelial neoplasia (HGPIN) and prostate cancer (PCa). Our recent work has demonstrated that (1) 15-LOX2 has multiple alternatively spliced isoforms and is a negative cell-cycle regulator in normal human prostate (NHP) epithelial cells; (2) 15-LOX2 in NHP cells is positively regulated by Sp1 and negatively regulated by Sp3; (3) 15-LOX2 in NHP cells may be partially involved in cell differentiation; (4) 15-LOX2 is cell-autonomously upregulated in cultured NHP cells and its induction is associated with NHP cell senescence; and (5) 15-LOX2 is a functional prostate tumor suppressor. Here we summarize these new findings to provide a concise view of the potential biological functions of 15-LOX2 in NHP cells and of its deregulation in PCa development.
Tang
Dean G
DG
Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park-Research Division, 1808 Park Rd. 1C, Smithville, TX 78957, United States. dtang@mdanderson.org
Bhatia
Bobby
B
Tang
Shaohua
S
Schneider-Broussard
Robin
R
D000328:Adult; D017398:Alternative Splicing; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D015820:Cadherins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation; D049108:Cell Enlargement; D016922:Cellular Senescence; D004847:Epithelial Cells / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology; D008297:Male; D011467:Prostate / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000503:physiopathology; D011944:Receptors, Androgen / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000502:physiology; D051705:Sp3 Transcription Factor / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D015820:Cadherins; D018797:Cell Cycle Proteins; D006893:Hydroxyeicosatetraenoic Acids; D011944:Receptors, Androgen; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D025521:Tumor Suppressor Proteins; D051705:Sp3 Transcription Factor; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase