Downregulation of key regulatory proteins in androgen dependent prostate tumor cells by oncolytic reovirus.
As prostate tumor cell growth depends on hormones, androgen ablation is an effective therapy for prostate cancer (PCa). However, progression of PCa cells to androgen independent growth (castrate resistant prostate cancer, CRPC) results in relapse and mortality. Hypoxia, a microenvironment of low oxygen that modifies the activity of PCa regulatory proteins including the androgen receptor (AR), plays a critical role in progression to CRPC. Therapies targeting hypoxia and the AR may lengthen the time to CRPC progression thereby increasing survival time of PCa patients. Mammalian Orthoreovirus (MRV) has shown promise for the treatment of prostate tumors in vitro and in vivo. In this study, we found that MRV infection induces downregulation of proteins implicated in CRPC progression, interferes with hypoxia-induced AR activity, and induces apoptosis in androgen dependent cells. This suggests MRV possesses traits that could be exploited to create novel therapies for the inhibition of progression to CRPC.
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011 , United States; Interdepartmental Genetics Program, Iowa State University, Ames, IA 50011, United States. Electronic address: pgupta@iastate.edu.
Pooja
P
Gupta-Saraf
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011 , United States; Biology Program, Iowa State University, Ames, IA 50011, United States. Electronic address: tmeseke@iastate.edu.
Tyler
T
Meseke
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011 , United States; Interdepartmental Genetics Program, Iowa State University, Ames, IA 50011, United States; Biology Program, Iowa State University, Ames, IA 50011, United States. Electronic address: clm@iastate.edu.
Cathy L
CL
Miller
D000728:Androgens / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D030102:Orthoreovirus, Mammalian / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; D051057:Proto-Oncogene Proteins c-akt; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
Akt; Androgen receptor; Hypoxia; PSA; Prostate cancer; Reovirus