Cell-cycle regulators cdk2ap1 and bicalutamide suppress malignant biological interactions between prostate cancer and bone cells

Olga Zolochevska, Marxa L. Figueiredo

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Introduction We examined whether the novel cell-cycle regulator cdk2-associated protein 1 (p12cdk2ap1 or cdk2ap1), recently shown to regulate prostate cancer cell cycle and apoptosis, could have the capacity to reduce invasiveness and/or reduce malignant biological interactions between prostate cancer and bone cells. We also examined whether combining two cell-cycle arrest stimuli, cdk2ap1 plus bicalutamide (or casodex, CDX), could help enhance inhibition of prostate cancer cell phenotypes. Methods We stably expressed cdk2ap1 in prostate cancer cell lines using lentiviral vectors, as well as several different co-culture assays to quantify cellular invasion, migration, and the effect of the treatments on interaction with the bone microenvironment. Results We have determined that cdk2ap1 can further augment the effects of CDX on cell-cycle arrest, growth inhibition, and cellular invasion. Using a coculture model, we observed that either cdk2ap1 or cdk2ap1/CDX combination were able to reduce chemotaxis towards osteoblasts, and also reduce the osteoblastic proliferative response to prostate cancer. Also modified by cdk2ap1 and CDX were several signaling pathways associated with prostate cancer/bone crosstalk mechanisms involved in prostate cancer progression. Conclusions These results suggest that either cdk2ap1 or the cdk2ap1/CDX combination hold promise in regulating prostate cancer growth and malignant phenotypes, and potentially also in reducing procarcinogenic interactions with a bone microenvironment model, restoring malignant phenotypes and signaling to a more benign state.

Original languageEnglish (US)
Pages (from-to)353-367
Number of pages15
JournalProstate
Volume71
Issue number4
DOIs
StatePublished - Mar 1 2011

Keywords

  • bicalutamide
  • bone interaction
  • cdk2ap1
  • cell-cycle regulation
  • prostate cancer
  • therapy

ASJC Scopus subject areas

  • Oncology
  • Urology

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