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

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 occurred 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= 0.008). There was no association between virus infection and TP53 nuclear accumulation (p = 0.5). However, a significant association was found between infection and MDM2 nuclear staining, and between infection and activated AKT (p = 0.04, p = 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.

journal_name

Int J Cancer

authors

Patel H,Polanco-Echeverry G,Segditsas S,Volikos E,McCart A,Lai C,Guenther T,Zaitoun A,Sieber O,Ilyas M,Northover J,Silver A

doi

10.1002/ijc.23028

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

2668-73

issue

12

eissn

0020-7136

issn

1097-0215

journal_volume

121

pub_type

杂志文章
  • Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study.

    abstract::To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 92...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23891

    authors: Dong CX,Deng DJ,Pan KF,Zhang L,Zhang Y,Zhou J,You WC

    更新日期:2009-01-15 00:00:00

  • Counteracting effects of dexamethasone and alpha 2-macroglobulin on inhibition of proliferation of normal and neoplastic rat hepatocytes by transforming growth factors-beta type 1 and type 2.

    abstract::Primary cultures of hepatocytes isolated from normal F-344 rats or from F-344 rats with hepatocellular carcinomas generated by a 2-step model of chemical carcinogenesis were used to determine if dexamethasone (DEX) or alpha 2-macroglobulin (alpha 2M) modify the ability of transforming growth factors-beta type I (TGF-b...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910470223

    authors: Wollenberg GK,LaMarre J,Semple E,Farber E,Gauldie J,Hayes MA

    更新日期:1991-01-21 00:00:00

  • Long-term C-cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression in virus-infected leukocyte cultures.

    abstract::Regression of EB-virus-induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus-infected T-cell-depleted population in order to e...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230505

    authors: Rickinson AB,Moss DJ,Pope JH

    更新日期:1979-05-15 00:00:00

  • Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer.

    abstract::Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32920

    authors: Lopès A,Billard E,Casse AH,Villéger R,Veziant J,Roche G,Carrier G,Sauvanet P,Briat A,Pagès F,Naimi S,Pezet D,Barnich N,Dumas B,Bonnet M

    更新日期:2020-06-01 00:00:00

  • The molecular rationale of Src inhibition in colorectal carcinomas.

    abstract::Src has been one of the most studied proto-oncogenes. The cellular Src (c-Src) holds a critical role in several human malignancies and has emerged as a key factor that promotes tumor progression during the multistep process of colorectal cancer (CRC) pathogenesis. The robust activation of Src in CRC of aggressive phen...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.28299

    authors: Gargalionis AN,Karamouzis MV,Papavassiliou AG

    更新日期:2014-05-01 00:00:00

  • Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient conditions.

    abstract::Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to identify survival and stress pathways whose inhibition could synergize ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29303

    authors: Saeed K,Östling P,Björkman M,Mirtti T,Alanen K,Vesterinen T,Sankila A,Lundin J,Lundin M,Rannikko A,Nordling S,Mpindi JP,Kohonen P,Iljin K,Kallioniemi O,Rantala JK

    更新日期:2015-06-01 00:00:00

  • Alcohol consumption and colon cancer prognosis among participants in north central cancer treatment group phase III trial N0147.

    abstract::Alcohol consumption is associated with a modest increased risk of colon cancer, but its relationship with colon cancer survival has not been elucidated. Using data from a phase III randomized adjuvant trial, we assessed the association of alcohol consumption with colon cancer outcomes. Patients completed a risk factor...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30135

    authors: Phipps AI,Shi Q,Limburg PJ,Nelson GD,Sargent DJ,Sinicrope FA,Chan E,Gill S,Goldberg RM,Kahlenberg M,Nair S,Shields AF,Newcomb PA,Alberts SR,Alliance for Clinical Trials in Oncology.

    更新日期:2016-09-01 00:00:00

  • Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.

    abstract::The major goal in cancer immunotherapy is the induction of tumor-specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a m...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:

    authors: Furumoto K,Arii S,Yamasaki S,Mizumoto M,Mori A,Inoue N,Isobe N,Imamura M

    更新日期:2000-09-01 00:00:00

  • IGFBP-3 prolongs the p53 response and enhances apoptosis following UV irradiation.

    abstract::Neoplastic transformation is characterised by an imbalance in favour of cell growth over programmed cell death (apoptosis). The tumour-suppressor gene p53, responsible for maintaining cell-cycle control, is mutated in the majority of human cancers. Loss of function of the target genes of p53 are therefore important in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:

    authors: Hollowood AD,Lai T,Perks CM,Newcomb PV,Alderson D,Holly JM

    更新日期:2000-11-01 00:00:00

  • Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells: direct and synergistic effects with transforming growth factor beta1.

    abstract::Tenascin-C (TN-C) and matrix metalloproteinases (MMPs) are highly expressed in cancer tissues and probably promote cell migration during cancer progression. TN-C and MMPs are often co-localized in areas of active tissue remodeling in pathologic conditions, suggesting reciprocal regulation. To investigate whether TN-C ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.11037

    authors: Kalembeyi I,Inada H,Nishiura R,Imanaka-Yoshida K,Sakakura T,Yoshida T

    更新日期:2003-05-20 00:00:00

  • Elevated expression of eIF4E in confined early breast cancer lesions: possible role of hypoxia.

    abstract::The translation-initiation factor eIF4E is rate-limiting for protein synthesis, and its over-expression results in oncogenic transformation of mammalian cells. eIF4E facilitates the synthesis of several powerful tumor angiogenic factors (FGF-2 and VEGF) by selectively enhancing their translation. In breast carcinomas,...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990209)80:4<516::aid-ijc

    authors: DeFatta RJ,Turbat-Herrera EA,Li BD,Anderson W,De Benedetti A

    更新日期:1999-02-09 00:00:00

  • The immunospecificity of altered initial arrest patterns of circulating cancer cells in tumor-bearing mice.

    abstract::The early arrest patterns of a methylcholanthrene-induced fibrosarcoma were determined after injection of 125IUdR-labelled cells into the systemic circulation of mice bearing transplanted lymphosarcomas, and of normal animals. Similar experiments were performed using radiolabelled lymphosarcoma cells and normal or fib...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910180608

    authors: Weiss L,Glaves D

    更新日期:1976-12-15 00:00:00

  • Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue.

    abstract::Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions use...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910340111

    authors: Gudnason V,Ingvarsson S,Jonasdottir A,Andresdottir V,Egilsson V

    更新日期:1984-07-15 00:00:00

  • An in vitro model of intra-epithelial expansion of transformed urothelial cells.

    abstract::Replacement of normal urothelium by pre-cancerous epithelium may explain the high recurrence rate of human bladder cancer. An in vitro model was designed in order to study the mechanisms of expansion of transformed urothelial cells at the expense of normal urothelium. For this purpose, mouse bladder explants were allo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910540520

    authors: Rebel JM,de Boer WI,Thijssen CD,Vermey M,Zwarthoff EC,van der Kwast TH

    更新日期:1993-07-09 00:00:00

  • Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States.

    abstract::Squamous cell carcinoma of the conjunctiva (SCCC) has been associated with HIV infection in equatorial Africa, but the evidence for association with HIV in developed countries, where SCCC is rarer, is controversial. We investigated the risk for SCCC and other eye cancers in the updated U.S. HIV/AIDS Cancer Match Regis...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23384

    authors: Guech-Ongey M,Engels EA,Goedert JJ,Biggar RJ,Mbulaiteye SM

    更新日期:2008-06-01 00:00:00

  • Human papillomavirus genotypes and HPV16 variants in penile carcinoma.

    abstract::The causative role of human papillomaviruses (HPV) and HPV16 variants has been extensively studied in uterine cervix dysplastic lesions and invasive carcinoma; few such studies, however, have been performed in penile tumors. We have investigated HPV genotype and HPV16 variant distribution on 41 penile cancer biopsies ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23062

    authors: Tornesello ML,Duraturo ML,Losito S,Botti G,Pilotti S,Stefanon B,De Palo G,Gallo A,Buonaguro L,Buonaguro FM

    更新日期:2008-01-01 00:00:00

  • No evidence for simian virus 40 DNA sequences in malignant non-Hodgkin lymphomas.

    abstract::DNA sequences coding for simian virus 40 (SV40) large T antigen have been detected at different frequencies in human non-Hodgkin's lymphomas (NHL) by PCR techniques as well as immunohistochemistry. A highly sensitive quantitative real-time PCR specific for a sequence of SV40 large T antigen was established to test whe...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21346

    authors: Schüler F,Dölken SC,Hirt C,Dölken MT,Mentel R,Gürtler LG,Dölken G

    更新日期:2006-01-15 00:00:00

  • Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-gamma in melanoma cell cultures established from CNS lesions.

    abstract::In advanced stages of malignant melanoma (MM), metastases to the CNS are frequently observed. Few results are available on trophic factors and immunological features involved in the process of invasion and adhesion of circulating metastatic cells into the CNS. A direct comparison of remote metastases found in differen...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990924)83:1<135::aid-ijc

    authors: Geertsen R,Zenklusen R,Kamarashev J,Burg G,Dummer R

    更新日期:1999-09-24 00:00:00

  • Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum-induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer.

    abstract::Evidence indicates that acquired resistance of cancers to chemotherapeutic agents can occur via epigenetic mechanisms. Down-regulation of expression of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in the biosynthesis of arginine, has been associated with the development of platinum resistance in ovari...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24546

    authors: Nicholson LJ,Smith PR,Hiller L,Szlosarek PW,Kimberley C,Sehouli J,Koensgen D,Mustea A,Schmid P,Crook T

    更新日期:2009-09-15 00:00:00

  • Host immune potentiation of drug responses to a murine mammary adenocarcinoma. II. Effect of melphalan therapy on the host immune system.

    abstract::The role of chemotherapy in influencing tumor-specific immunity to a mouse mammary adenocarcinoma was investigated. By studying different stages of tumor growth we were able to identify several factors important to drug-induced tumor regression: (1) antibody response, (2) delayed hypersensitivity, (3) sensitivity of t...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910180512

    authors: Radov LA,Korn JH,Haskill JS

    更新日期:1976-11-15 00:00:00

  • Conundrums in screening for cancer.

    abstract::Screening for cancer has to be carefully organized for maximum effectiveness, and introduced in full understanding of the natural history of the disease. There are major potential harms as well as benefits from screening. The current state of art for breast, cervix and prostate cancer screening is reviewed, only for b...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.25081

    authors: Miller AB

    更新日期:2010-03-01 00:00:00

  • Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome.

    abstract::Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes such as loss of heterozygosity (LOH) on human chromosome 18q21. This chromosomal region maps a gene cluster coding for a family of intracellular serine protease inhibitors (serpins), including SERPINB13. As SERPI...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24507

    authors: de Koning PJ,Bovenschen N,Leusink FK,Broekhuizen R,Quadir R,van Gemert JT,Hordijk GJ,Chang WS,van der Tweel I,Tilanus MG,Kummer JA

    更新日期:2009-10-01 00:00:00

  • Patterns of growth and differentiation in the colon carcinoma cell line LIM 1863.

    abstract::The LIM 1863 colon carcinoma cell line grows in the form of morphologically and functionally organized organoids. Cells are arranged around a central lumen with a brush border and nuclei are polarized to the periphery. The organoids contain 3 morphological cell types (columnar, goblet and caveolated cells). By agar cl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910500515

    authors: Hayward IP,Whitehead RH

    更新日期:1992-03-12 00:00:00

  • Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth.

    abstract::Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. We have shown that flavokawain B (FKB), a kava chalcone, is about 4- to 12-fold more effective in reduc...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25210

    authors: Tang Y,Li X,Liu Z,Simoneau AR,Xie J,Zi X

    更新日期:2010-10-15 00:00:00

  • Reduced allergy and immunoglobulin E among adults with intracranial meningioma compared to controls.

    abstract::Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study partici...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25858

    authors: Wiemels JL,Wrensch M,Sison JD,Zhou M,Bondy M,Calvocoressi L,Black PM,Yu H,Schildkraut JM,Claus EB

    更新日期:2011-10-15 00:00:00

  • Nicotine modulates the effects of retinoids on growth inhibition and RAR beta expression in lung cancer cells.

    abstract::Epidemiological and animal studies have demonstrated that vitamin A and its natural and synthetic derivatives, retinoids, are effective agents in preventing the development of tobacco-associated cancers. Unfortunately, clinical trials of retinoids on cigarette smokers have shown lack of efficacy in preventing lung can...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10304

    authors: Chen GQ,Lin B,Dawson MI,Zhang XK

    更新日期:2002-05-10 00:00:00

  • Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

    abstract::Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29806

    authors: Parada H Jr,Wolff MS,Engel LS,White AJ,Eng SM,Cleveland RJ,Khankari NK,Teitelbaum SL,Neugut AI,Gammon MD

    更新日期:2016-02-01 00:00:00

  • Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort.

    abstract::Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox pr...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32112

    authors: Zeinomar N,Phillips KA,Daly MB,Milne RL,Dite GS,MacInnis RJ,Liao Y,Kehm RD,Knight JA,Southey MC,Chung WK,Giles GG,McLachlan SA,Friedlander ML,Weideman PC,Glendon G,Nesci S,kConFab Investigators.,Andrulis IL,Buys SS

    更新日期:2019-07-15 00:00:00

  • A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

    abstract::Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (S...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.25786

    authors: Harlid S,Ivarsson MI,Butt S,Hussain S,Grzybowska E,Eyfjörd JE,Lenner P,Försti A,Hemminki K,Manjer J,Dillner J,Carlson J

    更新日期:2011-10-01 00:00:00

  • Angiogenic potential of malignant and non-malignant human breast tissues in an in vivo angiogenesis model.

    abstract::Tumors need to acquire an angiogenic phenotype for outgrowth and metastasis formation. Limited information on the angiogenic potential of specific tissues, especially human breast tissues is available. Here we describe an in vivo model, using the dorsal skin fold chamber in immunodeficient nude mice, where various tis...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980729)77:3<455::aid-ijc

    authors: Lichtenbeld HC,Barendsz-Janson AF,van Essen H,Struijker Boudier H,Griffioen AW,Hillen HF

    更新日期:1998-07-29 00:00:00