Expression pattern of the AP-1 family in endometrial cancer: correlations with cell cycle regulators

Bamberger, Ana‐Maria; Milde‐Langosch, Karin; Rössing, Elena; Goemann, Christoph; Löning, Thomas

doi:10.1007/s004320100255

Cited by 65 publications

(57 citation statements)

References 18 publications

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“…Several of these proteins (IRS2, Tensin-3͞TEM6, BCAR3, and ␤-catenin) are involved in cytoplasmic signaling. This group, as well as the transcriptional activator Jun-C͞D, are known to either be up-regulated or more active in some cancer cells (22)(23)(24)(25)(26)(27)(28)(29). Thus, the phosphopeptides displayed on cancer cells and not JY BLCL are preferentially derived from source proteins associated with cytoplasmic signaling pathways and cellular transformation.…”

Section: Resultsmentioning

confidence: 99%

Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy

Zarling

Polefrone

Evans

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

169

217

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Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8 ؉ T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8 ؉ T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.tandem mass spectrometry ͉ immobilized metal-affinity chromatography

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Section: Resultsmentioning

confidence: 99%

Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy

Zarling

Polefrone

Evans

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

169

217

View full text Add to dashboard Cite

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“…for c-ras Ha activation observed in earlier KA studies (Corominas et al, 1989), exhibiting moderate elevation in MAP kinase signalling (Parsons, 2004;Downward, 2004;Karin, 1995) and overexpression of cyclin D1 (Bamberger et al, 2001;Burnworth et al, 2006) or cyclin E2 (Di Cristofano et al, 2001;Weng et al, 2001). Incremental increases in keratinocyte proliferation culminated in very high BrdU labelling indices in papillomatous KA histotypes, with typical delays in expression of differentiation markers and the appearance of focal keratin K13 expression, an early marker of tumour progression (Greenhalgh et al, 1995).…”

Section: Hk1fos/δ5ptenmentioning

confidence: 87%

“…HK1.fos papillomas (Fig. 5, PAP lane) exhibited increased cyclin D1 and cyclin E2 expression (Bamberger et al, 2001), together with very high levels of activated P-ERKs 1/2 expression (Fig. 4, lanes P, HP and N), which suggested that MAP kinase signalling during wound-promoted HK1.fos papillomatogenesis facilitated escape from AKT-linked countermeasures (above) and restored P-AKT activity (Segrelles et al, 2006).…”

Section: Hk1fos/δ5ptenmentioning

confidence: 90%

“…Given recent glioma studies where PTEN wt inhibits AP1 activity via reduced AKT signalling (Koul et al, 2007) and closes the links between PTEN/p53 loss and AP1 status (Wang et al, 2005), PTEN wt may act to limit Fos-mediated/p53-negative keratinocyte proliferation. Hence, the lack of P-AKT in hyperplastic HK1.fos epidermis delayed papilloma formation, which required TPA/wound promotion (Greenhalgh et al, 1993b(Greenhalgh et al, , 1995 to induced high P-ERK1/2 expression (Karin, 1995;Schlingemann et al, 2003), increase cyclin D1 and cyclin E2 (Bamberger et al, 2001), and restore P-AKT levels (Gonzales and Bowden, 2002).…”

Section: Hk1fos/δ5ptenmentioning

confidence: 99%

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Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21WAF-induced differentiation triggered by GSK3β inactivation and reduced AKT activity

Yao

Alexander

Quinn

et al. 2008

Journal of Cell Science

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To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate Pten function (K14.cre/Δ5Ptenflx) in mouse epidermis expressing activated Fos (HK1.Fos). RU486-treated HK1.Fos/Δ5Ptenflx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas, rather than to carcinomas, owing to re-expression of high p53 and p21WAF levels. Despite elevated MAP kinase activity, cyclin D1 and cyclin E2 overexpression, and increased AKT activity that produced areas of highly proliferative papillomatous keratinocytes, increasing levels of GSK3β inactivation induced a novel p53/p21WAF expression profile, which subsequently halted proliferation and accelerated differentiation to give the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3β-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This increase in expression reduced activated AKT expression and released inhibition of p21WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1 alongside premature filaggrin and loricrin expression. Thus, Fos synergism with Pten loss elicited a benign tumour context where GSK3β-induced p53/p21WAF expression continually switched AKT-associated proliferation into differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21WAF, otherwise deregulated Fos, Akt and Gsk3β associate with malignant progression.

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“…In osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and adverse outcome (Gamberi et al, 1998;Bamberger et al, 2001). In a comparative analysis between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions (Prusty and Das, 2005).…”

mentioning

confidence: 99%

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

et al. 2008

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Members of the Fos protein family dimerise with Jun proteins to form the AP-1 transcription factor complex. They have a central function in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumour progression. We analysed the expression of c-Fos, FosB, Fra-1 and Fra-2 to investigate the function of Fos transcription factors in ovarian cancer. A total of 101 patients were included in the study. Expression of Fos proteins was determined by western blot analysis, quantified by densitometry and verified by immunohistochemistry. Reduced c-Fos expression was independently associated with unfavourable progression-free survival (20.6, 31.6 and 51.2 months for patients with low, moderate and high c-Fos expression; P ¼ 0.003) as well as overall survival (23.8, 46.0 and 55.5 months for low, moderate and high c-Fos levels; P ¼ 0.003). No correlations were observed for FosB, Fra-1 and Fra-2. We conclude that loss of c-Fos expression is associated with tumour progression in ovarian carcinoma and that c-Fos may be a prognostic factor. These results are in contrast to the classic concept of c-Fos as an oncogene, but are supported by the recently discovered tumour-suppressing and proapoptotic function of c-Fos in various cancer types.

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Expression pattern of the AP-1 family in endometrial cancer: correlations with cell cycle regulators

Cited by 65 publications

References 18 publications

Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy

Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy

Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21WAF-induced differentiation triggered by GSK3β inactivation and reduced AKT activity

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

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