mdm2 mRNA expression is associated with survival in ovarian cancer

Berno, Tamara; Hengstler, Jan G.; Laubscher, Silke; Meinert, Rolf; Oesch, Franz; Weikel, W.; Knapstein, P.; Becker, Roger

doi:10.1002/(sici)1097-0215(19970822)74:4<438::aid-ijc13>3.0.co;2-5

Cited by 34 publications

(24 citation statements)

References 18 publications

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“…MDM2 mRNA expression was not associated with survival of any FIGO stage of ovarian cancer but was associated with the clinical outcome of FIGO stage III and IV patients (Tanner et al, 1997). Our present findings are similar to those of Tanner et al (1997), indicating that MDM2 mRNA expression is a favorable prognostic factor in NSCLC.…”

Section: Discussionsupporting

confidence: 76%

“…In this study, we tested whether the presence or absence of MDM2 mRNA was a suitable prognostic factor to predict the clinical outcome of NSCLC. To date, the use of MDM2 mRNA to predict the survival rate after chemotherapy has been reported only in ovarian cancer (Tanner et al, 1997). Our previous study (Wang et al, 1998) demonstrated high frequencies of deletion mutation in Taiwanese NSCLC and that this mutation was correlated with p53 immunostaining.…”

mentioning

confidence: 94%

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MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

Ko¹,

Cheng²,

Shu³

et al. 2000

Int. J. Cancer

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Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 94%

MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

Ko¹,

Cheng²,

Shu³

et al. 2000

Int. J. Cancer

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“…Apart from these reports, the ring domain of MDM2 has been shown to induce growth arrest (23). Consistent with these observations, several laboratories reported that overexpression of MDM2 is a favorable prognostic marker in cancer (24)(25)(26)(27).…”

Section: Introductionsupporting

confidence: 59%

The Growth Arrest Function of the Human Oncoprotein Mouse Double Minute-2 Is Disabled by Downstream Mutation in Cancer Cells

2005

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We have reported earlier that ectopic expression of mouse double minute-2 (MDM2) induces G 1 arrest in normal cells. To explain occasional overexpression of MDM2 in cancer cells, we searched for deletion or substitution mutation in the growth suppressor domains of MDM2 in several breast cancer cell lines that overexpress the oncoprotein. Our results suggest the absence of alteration (deletion or substitution) in the open reading frame of MDM2 transcripts in such cells. Because the breast cancer cell line MCF-7 overexpresses MDM2, we isolated the full-length MDM2 transcript from this cell line. The MDM2 cDNA synthesized from transcripts isolated from MCF-7 cells inhibited G 1 to S phase transition in normal human diploid cells such as WI38, suggesting that the genetic alterations in breast cancer cells that overexpress MDM2 disable the growth arrest function of the oncoprotein. Consistently, overexpression of full-length MDM2 in MCF-7 cells over its high endogenous level did not inhibit G 1 -S transition efficiently. Although MDM2 overexpression was accompanied by CDK4 overexpression or absence of cdk4 inhibitor p16 in most breast cancer cells, we found remarkably high levels of cyclin A rather than cyclin E in these cells. Ectopic expression of cyclin A released MDM2-mediated inhibition of G 1 -S transition in normal human diploid WI38 cells. We propose that cancer cells expressing high levels of cyclin A escape MDM2-mediated G 1 arrest, which may account for a selective growth advantage over normal cells. (Cancer Res 2005; 65(5): 1839-48)

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“…Although a higher mdm2 -mRNA expression was associated with a better prognosis in patients with ovarian carcinomas (24), several publications describe a correlation between a high HDM2 transcript level and poor outcome for different cancer patients (reviewed in ref. 23).…”

Section: Discussionmentioning

confidence: 99%

Association of HDM2 Transcript Levels with Age of Onset and Prognosis in Soft Tissue Sarcomas

Täubert

Bartel

Greither

et al. 2008

Molecular Cancer Research

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The p53 stress response is crucial for the prevention of tumor formation. The oncogene HDM2 is one of the key negative regulators of p53 and is a central node in the p53 pathway. P53 and HDM2 form an oscillating feedback loop. HDM2 expression is regulated by different promoters. To evaluate its clinical relevance, we determined the levels of HDM2 transcripts originating from the constitutive P1 and p53-sensitive P2 promoter in 133 soft tissue sarcomas and correlated the results with the age of diagnosis and the patients' outcome. We show that only high levels of the HDM2-P1 transcript but not the P2 transcript are associated with an 11-year earlier age of onset (50.5 years) compared with low P1 levels (61.5 years; P < 0.0001, t test). In addition, low P1 and P2 mRNA expression levels were independent predictors of poor outcome for patients with soft tissue sarcomas (low P1: relative risk, 3.7; P < 0.0001; low P2: relative risk, 2.5; P = 0.001). A change in the expression levels of the HDM2 transcripts originating from the two HDM2 promoters could disrupt the oscillating P53-HDM2 feedback loop in a way that elevated levels of HDM2-P1 transcript are associated with an earlier age of tumor onset and that reduced levels of HDM2-P1 or HDM2-P2 transcripts are correlated with poor prognosis of patients with soft tissue sarcomas. (Mol Cancer Res 2008;6(10):1575 -81)

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mdm2 mRNA expression is associated with survival in ovarian cancer

Cited by 34 publications

References 18 publications

MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

The Growth Arrest Function of the Human Oncoprotein Mouse Double Minute-2 Is Disabled by Downstream Mutation in Cancer Cells

Association of HDM2 Transcript Levels with Age of Onset and Prognosis in Soft Tissue Sarcomas

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