Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma

Patel, Heena, Polanco-Echeverry, Guadalupe, Segditsas, Stefania, Volikos, Emmanouil, McCart, Amy, Lai, Cecilia, Guenther, Thomas, Zaitoun, Abed, Ilyas, Mohammed, Northover, John and Silver, Anrew (2007) Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma. International Journal of Cancer, 121 12: 2668-2673. doi:10.1002/ijc.23028

Author Patel, Heena
Polanco-Echeverry, Guadalupe
Segditsas, Stefania
Volikos, Emmanouil
McCart, Amy
Lai, Cecilia
Guenther, Thomas
Zaitoun, Abed
Ilyas, Mohammed
Northover, John
Silver, Anrew
Title Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2007-12
Sub-type Article (original research)
DOI 10.1002/ijc.23028
Volume 121
Issue 12
Start page 2668
End page 2673
Total pages 6
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Formatted abstract
Human papilloma virus (HPV) infection is considered as an important aetiological factor for anal squamous cell carcinoma (ASCC) but is not sufficient for tumour progression. This carcinoma is poorly understood at the molecular level. Using the largest cohort of cases to date we investigated the molecular mechanisms underlying ASCC development, in particular the roles of TP53, MDM2 and AKT. Viral infection in our cohort occured at high frequency (73%, 94/128) with HPV16 accounting for the majority (86%, 81/94) of infected cases. Only 4% (5/119) of ASCCs showed TP53 (exons 5–8) mutations, but a high frequency (91%, 100/110) of nuclear protein expression of TP53 was observed. There was a significant association (p < 0.001) between nuclear accumulation of TP53 and MDM2 protein although no MDM2 mutations were found, and copy number was normal. Cellular accumulation of phosphorylated-AKT was observed in 66% (82/125) of ASCCs and an association demonstrated between nuclear accumulation of MDM2 and activated AKT (p < 0.001). We observed a high frequency of copy number gain at PIK3CA (47%), and some coding sequence mutations (4%). Amplification of PIK3CA was associated with  presence of phosphorylated-AKT (p 5 0.008). There was no association between virus infection and TP53 nuclear accumulation (p 5 0.5). However, a significant association was found between infection and MDM2 nuclear staining, and between infection and activated AKT (p 5 0.04, p 5 0.01, respectively). We propose that activation of AKT, possibly through the PI3K-AKT pathway, is an important component of ASCC tumorigenesis that contributes to MDM2 and TP53 accumulation in the nucleus.
Keyword Anal cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 22 Jun 2011, 15:12:15 EST by System User on behalf of Institute for Molecular Bioscience