title: Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis.
abstract: BACKGROUND
  The interferon inducible Myxovirus (influenza virus) resistance A (MxA) is considered as a key mediator of the interferon-induced antiviral response. Mx proteins contain the typical GTP-binding motif and show significant homology to dynamin family of GTPases. Strong interaction of MxA with tubulin suggests that Mx proteins could be involved in mitosis. Studies have shown that MxA inhibit tumor motility/metastasis and virus induced apoptosis. However, the clear association between MxA expression and cancer remains unknown. Meta-analysis suggested that MxA expression was inversely correlated with prostate cancer (PCa). In this study, we demonstrate the expression MxA in PCa and its functional significance on the cancer phenotype.
  
  
  METHODS
  The expression of MxA protein in prostate cancer was examined by immuno-histochemistry. MxA was knocked down (shMxA) or over-expressed (pMxA) in DU145 or LNCaP PCa cell lines respectively. These cell lines were used to study proliferation, apoptosis, invasion, migration, and anchorage independent growth. Co-localization of MxA with tubulin was performed by immuno-cytochemistry following Docetaxel treatment.
  
  
  RESULTS
  The expression of MxA protein was significantly decreased in PCa as compared to the normal tissues. DU145 cells lacking MxA (DU145 + chMxA) showed significant increase in proliferation, associated with decreased expression of CDKN1A and B. Increased migration, anchorage independent growth in DU145 + shMxA cells was associated with increased MMP13 expression. Tubulin organization was also dependent on MxA expression. Tubulin polymerizing agents such as Docetaxel was less effective in promoting apoptosis in cells lacking MxA due to altered tubulin organization. Gain of MxA expression in LNCaP cells (LNCaP + pMxA) resulted in cell cycle arrest that was associated with increased expression of CDKN1A. MxA expression was also down-regulated by dihydrotestosterone in LNCaP cells.
  
  
  CONCLUSIONS
  MxA expression is inversely correlated with prostate cancer. Down-regulation of MxA in LNCaP cells by DHT suggests that MxA could play a significant role in disease progression. Loss of MxA expression results in increased metastasis and decreased sensitivity to Docetaxel suggesting that MxA expression could determine the outcome of chemo-therapeutic treatment. Additional studies will be required to fully establish the cross-talk between androgen receptor-IFN pathway in regulating MxA expression in the normal prostate and prostate cancer. Prostate 75:266-279, 2015. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Department of Biology, South Carolina State University, Orangeburg, South Carolina.
authors.forename: Shanora G
authors.initials: SG
authors.lastname: Brown
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Knowell
authors.forename: Aisha
authors.initials: A
authors.lastname: Hunt
authors.forename: Divya
authors.initials: D
authors.lastname: Patel
authors.forename: Sushma
authors.initials: S
authors.lastname: Bhosle
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D006801:Humans; D008297:Male; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D014404:Tubulin / Q000378:metabolism
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel
keywords: Docetaxel; MxA; prostate cancer