Nuclear iASPP may facilitate prostate cancer progression

Morris, E V; Cerundolo, L; Lu, M; Verrill, C; Fritzsche, F; White, M J; Thalmann, George; ten Donkelaar, C S; Ratnayaka, I; Salter, V; Hamdy, F C; Lu, X; Bryant, R J (2014). Nuclear iASPP may facilitate prostate cancer progression. Cell death & disease, 5(10), e1492. Nature Publishing Group 10.1038/cddis.2014.442

Preview

Text cddis2014442a.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (14MB) | Preview

One of the major challenges in prostate cancer (PCa) research is the identification of key players that control the progression of primary cancers to invasive and metastatic disease. The majority of metastatic PCa express wild-type p53, whereas loss of p63 expression, a p53 family member, is a common event. Here we identify inhibitor of apoptosis-stimulating protein of p53 (iASPP), a common cellular regulator of p53 and p63, as an important player of PCa progression. Detailed analysis of the prostate epithelium of iASPP transgenic mice, iASPP(Δ8/Δ8) mice, revealed that iASPP deficiency resulted in a reduction in the number of p63 expressing basal epithelial cells compared with that seen in wild-type mice. Nuclear and cytoplasmic iASPP expression was greater in PCa samples compared with benign epithelium. Importantly nuclear iASPP associated with p53 accumulation in vitro and in vivo. A pair of isogenic primary and metastatic PCa cell lines revealed that nuclear iASPP is enriched in the highly metastatic PCa cells. Nuclear iASPP is often detected in PCa cells located at the invasive leading edge in vivo. Increased iASPP expression associated with metastatic disease and PCa-specific death in a clinical cohort with long-term follow-up. These results suggest that iASPP function is required to maintain the expression of p63 in normal basal prostate epithelium, and nuclear iASPP may inactivate p53 function and facilitate PCa progression. Thus iASPP expression may act as a predictive marker of PCa progression.

Interest & Impact

Downloads

139 since deposited on 26 Feb 2015
10 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item