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Published on: December 7, 2017
Investigation of mRNA Expression Levels of Tip60 and Related DNA Repair Genes in Molecular Subtypes of Breast Cancer
Ece Miser-Salihoglu1, Semra Demokan2, Hasan Karanlik3
1Faculty of Pharmacy, Department of Biochemistry, Gazi University, Ankara, Turkey.
Introduction:
Studies in breast cancer (BC) have been shown that many tumor cells carry mutations that disrupt the DNA damage response mechanism. In eukaryotic cells, the overexpression or deprivation of DSBs repair genes is linked closely to a higher risk of cancer.
Patients And Methods:
In this study, mRNA expression levels of some genes, such as Tip60, ATM, p53, CHK2, BRCA1, H2AX, which are associated with DNA damage repair, were measured using RT-PCR method in tumor and matched-normal tissues of 58 patients with BC.
Results:
According to the study results, 55% in Tip60, 59% in ATM, 57% in BRCA1, 48% in H2AX, 66% in CHK2, and 43% in p53 decreased in tumor tissue of patients compared to the matched normal tissue. When evaluated according to molecular subtypes, expression of all genes in the pathway was found significantly higher in normal tissues than in tumor tissues especially in Luminal B and Luminal B+HER2 groups. One of the most important results of the study is that CHK2 mRNA expressions in normal tissues were higher than tumor tissue in 90% of patients in Luminal B and Luminal B-HER2 + groups. This is the first study showing DNA repair genes' expressions in molecular subtypes of breast cancer. In general, the decrease in the expression of DNA damage repair genes in tumor tissue indicates that these genes may have a role in the development of BC. Our study results also suggest that CHK2 may be a candidate marker in the molecular classification of breast cancer.
Insights
This study found decreased DNA damage repair gene expression in breast cancer (BC) tissues compared to normal tissues, particularly in Luminal B subtypes. CHK2 (Checkpoint Kinase 2) may serve as a marker for BC molecular classification.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations disrupting DNA damage response mechanisms are common in breast cancer (BC).
- Dysregulation of DNA double-strand break (DSB) repair genes is linked to increased cancer risk.
Purpose of the Study:
- To investigate the mRNA expression levels of key DNA damage repair genes in BC tumor tissues versus matched normal tissues.
- To analyze these expression patterns across different BC molecular subtypes.
Main Methods:
- Quantitative reverse transcription PCR (RT-PCR) was used to measure mRNA levels.
- Gene expression was compared between tumor and matched-normal tissues from 58 BC patients.
- Analysis included specific genes: Tip60, ATM, p53, CHK2, BRCA1, and H2AX.
Main Results:
- A significant decrease in mRNA expression for all studied DNA damage repair genes was observed in tumor tissues compared to normal tissues.
- Expression levels were particularly lower in Luminal B and Luminal B+HER2 molecular subtypes.
- CHK2 (Checkpoint Kinase 2) showed significantly higher expression in normal tissues than tumor tissues in 90% of patients within Luminal B and Luminal B-HER2+ groups.
Conclusions:
- The observed decrease in DNA repair gene expression suggests their potential role in BC development.
- CHK2 (Checkpoint Kinase 2) emerges as a potential candidate marker for the molecular classification of breast cancer.
