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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Thalmann, George

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-4889

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Katharina Morgenegg

Date Deposited:

26 Feb 2015 14:16

Last Modified:

05 Dec 2022 14:40

Publisher DOI:

10.1038/cddis.2014.442

PubMed ID:

25341046

BORIS DOI:

10.7892/boris.63412

URI:

https://boris.unibe.ch/id/eprint/63412

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