Expression levels of p53 and p73 isoforms in stage I and stage III ovarian cancer

Marabese, Mirko; Marchini, Sergio; Marrazzo, Eleonora; Mariani, Pietro; Cattaneo, Dario; Fossati, Roldano; Compagnoni, Anna; Signorelli, Mauro; Moll, Ute M.; Codegoni, Anna Maria; Broggini, Massimo

doi:10.1016/j.ejca.2007.10.011

Cited by 29 publications

(23 citation statements)

References 22 publications

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“…A significant correlation has been reported between overexpression of ∆N isoforms and a poor prognosis in cervical, colon and ovarian cancer (10)(11)(12)14), but not in CCA. The incidence of p53 gene mutations in ICC is approximately 41.6% (15), while there has been no report of mutation in p73.…”

Section: Introductionmentioning

confidence: 99%

“…Deletion of their N-terminal domains not only contributes to the loss of transactivation but also interferes with the transactivation of their full-length isoforms (TAp53, TAp63 and TAp73), via tetramerization of the deleted isoform and the full-length protein (9). Therefore, overexpression of the ∆N isoform proteins can inactivate the full-length p53 family proteins (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Nutthasirikul

Limpaiboon

Leelayuwat

et al. 2013

International Journal of Oncology

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Abstract. All p53 family members are expressed in several isoforms through alternative promoters and alternative splicing. However, the significance of these isoforms is not yet well understood in cholangiocarcinoma (CCA). In this study, we investigated the expression of p53, p63, p73 and their isoforms at the mRNA and protein levels in CCA. The overexpression of ∆133p53 was observed in the CCA cell lines and clinical specimens. Moreover, the high expression of ∆133p53/TAp53 correlated with short overall survival (p<0.001). Defective p53, including mutant and ∆Np53, was associated with poor prognosis (p<0.024). Multivariate analysis demonstrated that ∆133p53̸TAp53 and mutant p53 protein may be used as independent prognostic factors for CCA. To our knowledge, this is the first report of the use of ∆133p53̸TAp53 as a potential biomarker in CCA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Nutthasirikul

Limpaiboon

Leelayuwat

et al. 2013

International Journal of Oncology

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“…Thus, p53 transcripts altered at the N terminus do not fail to activate transcription of the reporter gene. In addition, the expression of the N-terminally truncated splice variants D40p53 and D133p53 has not correlated with clinicopathologic parameters and prognosis in 169 ovarian cancers (Marabese et al, 2008).…”

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confidence: 99%

Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer

et al. 2010

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5Ludwig Boltzmann Gesellschaft, Cluster Translational Oncology, Vienna, Austria Similar to p73, the tumor suppressor gene p53 is subject to alternative splicing. Besides p53DE6 and p53b, we identified p53f, p53d and p53e, arising from alternative splicing of exon 6 and intron 9, respectively. p53 splice variants were present in 18 of 34 ovarian cancer cell lines (52.9%) and 134 of 245 primary ovarian cancers (54.7%). p53d expression was associated with impaired response to primary platinum-based chemotherapy (P ¼ 0.032). Also, p53d expression constituted an independent prognostic marker for recurrence-free and overall survival (hazard ratio 1.854, 95% confidence interval 1.121-3.065, P ¼ 0.016; and hazard ratio 1.937, 95% confidence interval 1.177-3.186, P ¼ 0.009, respectively). p53b expression was associated with adverse clinicopathologic markers, that is, serous and poorly differentiated cancers (P ¼ 0.002 and P ¼ 0.008, respectively), and correlated with worse recurrence-free survival in patients exhibiting functionally active p53 (P ¼ 0.049). DN 0 p73 constituted the main N-terminally truncated p73 isoform and was preferentially found in ovarian cancer cell lines showing functionally active p53, supporting our hypothesis that N-terminally truncated p73 isoforms can alleviate the selection pressure for p53 mutations by the inhibition of p53 protein function.

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“…Automatic liquid handling station (epMotion 5075 LH; Eppendorf) and real-time PCR (ABI-7900; Applied Biosystems) were used as described (19,20). The comparative threshold cycle (C t ) method was used for the calculation of amplification fold as specified by the manufacturer.…”

Section: Real-time Reverse Transcription-pcr and Primer Designmentioning

confidence: 99%

Analysis of Gene Expression in Early-Stage Ovarian Cancer

Marchini

Mariani

Chiorino

et al. 2008

Clinical Cancer Research

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Purpose: Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression. Experimental Design:Tumors were obtained directly at surgery and immediately frozen in liquid nitrogen until analysis. Glass arrays containing 16,000 genes were used in a dual-color assay labeling protocol. Results: Unsupervised analysis identified eight major patient partitions, one of which was statistically associated to overall survival, grading, and histotype and another with grading and histotype. Supervised analysis allowed detection of gene profiles clearly associated to histotype or to degree of differentiation. No difference was found between borderline and grade 1tumors. As to recurrence, a subset of genes able to differentiate relapsers from nonrelapsers was identified. Among these, cyclin E and minichromosome maintenance protein 5 were found particularly relevant, as their expression was inversely correlated to progression-free survival (P = 0.00033 and 0.017, respectively). Conclusions: Specific molecular signatures define different histotypes and prognosis of stage I ovarian cancer. Mucinous and clear cells histotypes can be distinguished from the others regardless of tumor grade. Cyclin E and minichromosome maintenance protein 5, whose expression was found previously to be related to a bad prognosis of advanced ovarian cancer, appear to be potential prognostic markers in stage I ovarian cancer too, independent of other pathologic and clinical variables.

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Expression levels of p53 and p73 isoforms in stage I and stage III ovarian cancer

Cited by 29 publications

References 22 publications

Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer

Analysis of Gene Expression in Early-Stage Ovarian Cancer

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