TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancer

Langerød, Anita; Zhao, Hongjuan; Borgan, Ørnulf; Nesland, Jahn M.; Bukholm, Ida Rashida Khan; Ikdahl, Tone; Kåresen, Rolf; Børresen-Dale, Anne Lise; Jeffrey, Stefanie S.

doi:10.1186/bcr1675

Cited by 250 publications

(111 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result was supported by the previous studies that p27 of p21 family is an inhibitor of cyclin D1-CDK 4 and cyclin A-CDK 2 complexes, the increased expression inhibits the activity of cyclin D- CDK 4 [48]. p53 mutation is one of the most powerful prognostic markers in breast cancer and is a desirable target gene for therapeutic potential [49-51]. The upregulation of p53 suggested that galangin could inhibit the mutation of MCF-7 cells.…”

Section: Discussionsupporting

confidence: 70%

Galangin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Mitochondrial Pathway and Phosphatidylinositol 3-Kinase/Akt Inhibition

et al. 2018

View full text Add to dashboard Cite

Aims: The study aimed to investigate the molecular mechanism of inhibition of proliferation and apoptosis induction by galangin against MCF-7 human breast cancer cells. Methods: Cell Counting Kit-8 assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis. The expression level of apoptosis-related proteins (cleaved-caspase-9, cleaved-caspase-8, cleaved-caspase-3, Bad, cleaved-Bid, Bcl-2, Bax, p-phosphatidylinositol 3-kinase [PI3K], and p-Akt) and cell cycle-related proteins (cyclin D3, cyclin B1, cyclin-dependent kinases CDK1, CDK2, CDK4, p21, p27, p53) were evaluated by Western blotting. Results: Galangin increased the expression of Bax and decreased the expression of Bcl-2 in a concentration-dependent manner, inhibited cell viability, and induced apoptosis. Meanwhile, the expression of cleavage of caspase-9, caspase-8, caspase-3, Bid, and Bad increased significantly while the expression of p-PI3K and p-Akt proteins decreased. In addition, the protein levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated while the expression levels of p21, p27, and p53 were upregulated significantly. Conclusion: Galangin could suppress the viability of MCF-7 cells and induce cell apoptosis via the mitochondrial pathway and PI3K/Akt inhibition as well as cell cycle arrest.

show abstract

Section: Discussionsupporting

confidence: 70%

Galangin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Mitochondrial Pathway and Phosphatidylinositol 3-Kinase/Akt Inhibition

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Another favorable characteristic of the hypermethylated tumors was the observation that none of them had a p53 mutation. Mutated p53 was found to significantly correlate with a greater carcinogenic aggressiveness and worse OS of breast cancer patients (17,(36)(37)(38). Since p53 and BRCA1 are involved in a same cancer pathway, it could be speculated that the inactivation of the pathway does not require inactivation of both genes (inactivation of one gene may be sufficient).…”

Section: Discussionmentioning

confidence: 99%

Breast cancer patients with hypermethylation in the promoter of BRCA1 gene exhibit favorable clinical status

Krasteva¹,

Bozhanov²,

G³

et al. 2012

neo

View full text Add to dashboard Cite

Promoter hypermethylation was shown to be involved in human cancerogenesis through silencing gene expression. Several studies were dedicated to explore the frequency and clinical significance of BRCA1 hypermethylation in sporadic breast cancer to identify a specific molecular and clinico-pathological phenotype. However the available data are limited and rather too heterogeneous. In this study we investigated the level of methylation in the promoter region of BRCA1 and its correlation with clinico-pathological and molecular characteristics in a group of 135 Bulgarian patients. Methylation specific PCR was applied to determine methylation status of tumor samples. Clinical impact of BRCA1 hypermethylation was estimated using standard statistical methods including Fisher's exact and the Chi-squared tests, the Kaplan-Meier method, the univariate and multivariate Cox proportional hazards regression model. We found that hypermethylation was present in 17.04% of the cases (23/135). Patients with hypermethylation in BRCA1 displayed favorable clinical status as their tumors were smaller in size (P = 0.066), lacked p53 gene mutations (P = 0.073) and were of lobular type (P = 0.046). The presence of hypermethylation was weakly associated with better overall survival (P = 0.2) with a hazard ratio of 0.47 (95% CI 0.14-1.54, P = 0.213). Our study provides the first data on the BRCA1 hypermethylation of Bulgarian patients and contributes to elucidation of its clinical significance in sporadic breast cancer. Key words: Breast cancer, BRCA1, Hypermethylation, Clinicopathological characteristics, Overall survivalBreast cancer (BC) represents a major challenge to modern human oncology because of its high and constantly increasing frequency, and growing mortality and morbidity rate in women below the age of 45. Every year in Bulgaria, approximately 3600 women are diagnosed and about 1300 die of BC (1). The major risk factors are sex, age, family predisposition, as well as some reproductive and hormonal factors like early menarche and late menopause, late first childbirth, shorter breastfeeding period, use of oral contraceptives and hormone replacement therapy. Clinically BC is very heterogeneous, which is due to heterogeneity in disease mechanisms.BC results from accumulation of genetic and epigenetic changes in tumor suppressor genes and proto-oncogenes. Some of these genes -р53, PIK3CA, CHEK2, АТМ, HER2, are involved in the pathogenesis of different type of tumors. Others are specific only to breast/ovarian cancer -BRCA1 and BRCA2. A large number of studies demonstrate a correlation between the genetic/epigenetic status of BC related genes and clinicopathological characteristics of the patients. Such investigations could contribute to a more effective BC prevention and therapy, which will increase the survival rate and will significantly improve the quality of life of the patients. However, the results so far are contradictory and need further elucidation.BRCA1 (BReast CAncer susceptibility gene 1) tumor suppressor gene maps to 17...

show abstract

“…Similarly, in an analysis of LFS patients, germline missense mutations in TP53 have been shown to be associated with an earlier age of onset (;9 years) when compared with germline deletions in TP53, suggesting a gain-of-function effect of missense p53 mutants in human tumors (Bougeard et al 2008). In addition, multiple studies have also demonstrated that the mutational status of p53 is a strong predictor for poor outcomes in many types of human tumors, particularly breast cancer (Elledge et al 1993;Olivier et al 2006;Langerod et al 2007;Petitjean et al 2007a).…”

Section: Gain-of-function Hypothesismentioning

confidence: 99%

Mutant p53: one name, many proteins

Freed-Pastor¹,

Prives²

2012

Genes Dev.

1,055

1,198

View full text Add to dashboard Cite

There is now strong evidence that mutation not only abrogates p53 tumor-suppressive functions, but in some instances can also endow mutant proteins with novel activities. Such neomorphic p53 proteins are capable of dramatically altering tumor cell behavior, primarily through their interactions with other cellular proteins and regulation of cancer cell transcriptional programs. Different missense mutations in p53 may confer unique activities and thereby offer insight into the mutagenic events that drive tumor progression. Here we review mechanisms by which mutant p53 exerts its cellular effects, with a particular focus on the burgeoning mutant p53 transcriptome, and discuss the biological and clinical consequences of mutant p53 gain of function.

show abstract

TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancer

Cited by 250 publications

References 35 publications

Galangin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Mitochondrial Pathway and Phosphatidylinositol 3-Kinase/Akt Inhibition

Galangin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Mitochondrial Pathway and Phosphatidylinositol 3-Kinase/Akt Inhibition

Breast cancer patients with hypermethylation in the promoter of BRCA1 gene exhibit favorable clinical status

Mutant p53: one name, many proteins

Contact Info

Product

Resources

About