Mutation analysis of the MDM4gene in German breast cancer patients

Reincke, Scarlett; Govbakh, Lina; Wilhelm, Bettina; Hai-yan, Jin; Bogdanova, Natalia; Bremer, Michael; Karstens, Johann H.; Dörk, Thilo

doi:10.1186/1471-2407-8-52

Cited by 10 publications

(8 citation statements)

References 44 publications

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“…CK1 and CK2 are two protein kinases that participate in a wide variety of cellular processes, including DNA repair and cell cycle control. Genotyping of this polymorphims in breast cancer patients did not reveal a preferential association with this neoplasia 18. Further studies are necessary to confirm the association of this allele with cancer, in view of the paucity of data in the literature.…”

Section: Discussionmentioning

confidence: 76%

“…The frequency of MDM4 rs4252668C was significantly higher in controls than in patients. Analyses of larger samples might be revealing for understanding its relevance in cancer in view that rs4252668 is located within p53 binding domain of MDM4 , probably affecting p53 regulation; partial data indicated that this allele was not associated with an increased risk of breast cancer 18.…”

Section: Discussionmentioning

confidence: 99%

“…Genomic DNA was isolated from peripheral blood lymphocytes following a previously described protocol 19. MDM2 and MDM4 polymorphisms genotyping was carried out by PCR/RFLP analysis as previously described 9, 18, 20. Sequencing of randomly selected, amplified products was carried out for confirming genotypic data with an ABI PRISM 3100 automated platform (Applied Biosystems, Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

“…MDM4 protein also regulates pRB levels because pRB ubiquitination mediated by MDM2 is inhibited by MDM4, due to competition between MDM2 and MDM4 for ligation to the C‐terminal domain of pRB 8. MDM4 polymorphisms and mutations have been frequently studied due to their impact on TP53 and RB1 regulation and in association to risk of some cancer types, as is the case of rs4252668 or rs116197192 (c.458A>G) with breast cancer 18.…”

Section: Introductionmentioning

confidence: 99%

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Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Reis

Carvalho

Damasceno

et al. 2011

Pediatric Blood & Cancer

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Reis

Carvalho

Damasceno

et al. 2011

Pediatric Blood & Cancer

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“…As for Mdmx, there is no evidence for its involvement in heritable BrCa, 28 and in somatic BrCa reports of amplifications of the Mdmx gene vary 14 , 15 (apparently dependent on the designated threshold). Our results are consistent with low-frequency involvement of Mdm2 in luminal BrCa, but revealed high Mdmx protein levels in all the luminal BrCa cases ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting Mdmx to treat breast cancers with wild-type p53

et al. 2015

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The function of the tumor suppressor p53 is universally compromised in cancers. It is the most frequently mutated gene in human cancers (reviewed). In cases where p53 is not mutated, alternative regulatory pathways inactivate its tumor suppressive functions. This is primarily achieved through elevation in the expression of the key inhibitors of p53: Mdm2 or Mdmx (also called Mdm4) (reviewed). In breast cancer (BrCa), the frequency of p53 mutations varies markedly between the different subtypes, with basal-like BrCas bearing a high frequency of p53 mutations, whereas luminal BrCas generally express wild-type (wt) p53. Here we show that Mdmx is unexpectedly highly expressed in normal breast epithelial cells and its expression is further elevated in most luminal BrCas, whereas p53 expression is generally low, consistent with wt p53 status. Inducible knockdown (KD) of Mdmx in luminal BrCa MCF-7 cells impedes the growth of these cells in culture, in a p53-dependent manner. Importantly, KD of Mdmx in orthotopic xenograft transplants resulted in growth inhibition associated with prolonged survival, both in a preventative model and also in a treatment model. Growth impediment in response to Mdmx KD was associated with cellular senescence. The growth inhibitory capacity of Mdmx KD was recapitulated in an additional luminal BrCa cell line MPE600, which expresses wt p53. Further, the growth inhibitory capacity of Mdmx KD was also demonstrated in the wt p53 basal-like cell line SKBR7 line. These results identify Mdmx growth dependency in wt p53 expressing BrCas, across a range of subtypes. Based on our findings, we propose that Mdmx targeting is an attractive strategy for treating BrCas harboring wt p53.

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Two novel cSNPs of weaver gene in Chinese indigenous goat and their associations with milk yield

Chen

Lan

et al. 2009

Mol Biol Rep

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Weaver gene plays an essential physiological role in the function of many organs, including brain, heart, kidney and endocrine cells, and also in the regulation of insulin secretion by glucose and/or neurotransmitters. Thus, weaver gene is an important potential candidate gene effecting on performance traits. The objective of this study was to detect the genetic variation of five loci within weaver gene by PCR-SSCP, DNA sequencing and forced PCR-RFLP methods in 1,019 Chinese indigenous goats. Two novel coding SNPs (XM_598993:m.864G>A; XM_598993:m.1224T>A) locating on P3 and P4 loci were identified and detected by MluI and AsuII forced PCR-RFLP, respectively. In the MluI analysis, the frequencies of goat MluI-A allele in the analyzed populations were 0.226, 0.248, 0.096 and 0.088 for XNSN, GZ, SBWC and XJWC, respectively. Genotypic frequencies were found to be significantly different in four breeds (chi2 = 75.842, df = 6, P < 0.001); In the AsuII analysis, the frequencies of goat AsuII-A allele in the analyzed populations were 0.584, 0.441, 0.073 and 0.063 for XNSN, GZ, SBWC and XJWC, respectively. Genotypic frequencies were found to be significantly different among four breeds (chi2 = 399.464, df = 6, P < 0.001). The frequencies of allele MluI-A and AsuII-A in XNSN and GZ populations were significantly higher than those of SBWC and XJWC goats. Association analysis with adjusted milk yield in the XNSN breed indicated that the animals with AsuII-AA genotype owned significantly higher adjusted milk yield than the ones with AsuII-TT genotype in the second lactation (P < 0.05). The observation suggested that the allele "AsuII-A" had the positive effects on adjusted milk yield in the second lactation.

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Mutation analysis of the MDM4gene in German breast cancer patients

Abstract: Background: MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.

Cited by 10 publications

References 44 publications

Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Targeting Mdmx to treat breast cancers with wild-type p53

Two novel cSNPs of weaver gene in Chinese indigenous goat and their associations with milk yield

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