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- Title
Differential mRNA expression of the main apoptotic proteins in normal and malignant cells and its relation to in vitro resistance.
- Authors
Vazanova, Andrea; Jurecekova, Jana; Balharek, Tomas; Marcinek, Juraj; Stasko, Jan; Dzian, Anton; Plank, Lukas; Zubor, Pavol; Racay, Peter; Hatok, Jozef
- Abstract
Background: Apoptosis plays an important role in the development and homeostasis of multicellular organisms and its deregulation may result in many serious diseases, including cancer. Now it is clear that some oncogenic mutations disrupt apoptosis, leading to tumour initiation, progression or metastasis. Here, expression of apoptotic genes in context of drug resistance was investigated. Methods: We examined total of 102 samples from leukemic patients (n = 60) and patients with solid tumours (n = 42). We used RT-PCR to determine the levels of mRNA expression and the in vitro chemoresistance of leukemic cells was evaluated using the MTT assay. Results: We found statistically significant increase in mRNA expression of all investigated proteins (p53, BAX, Bcl-2 and Bcl-XL) between the leukemia samples and leukocytes from healthy volunteers. We did not find any significant difference in mRNA levels among the solid tumour samples. Notably, we showed a significant positive correlation in both leukemic and solid tumour patient groups between <italic>p53</italic> and <italic>BAX</italic> mRNA. We found that the highest values for the <italic>Bcl</italic>-<italic>2/BAX</italic> ratio were in solid tumours in comparison to leukemic cells or normal leukocytes. Moreover, we assessed the impact of <italic>p53</italic> and <italic>BAX</italic> mRNA levels on the sensitivity of the leukemic cells to selected cytostatics. Conclusions: Elevated levels of <italic>p53</italic> and <italic>BAX</italic> mRNA may indicate cellular response to possible changes in genomic DNA integrity associated with malignant transformation. We suggest that the <italic>BAX</italic> gene is regulated by the p53 protein but the initiation of apoptosis through the transcription activation of <italic>BAX</italic> is blocked by the high levels <italic>of Bcl</italic>-<italic>2</italic>. Given that the apoptosis resistance mechanisms are different among oncological patients as well as stages of identical malignancy cases, personalized and specific combination therapy is proposed to be more effective in clinical application.
- Subjects
CELL proliferation; PROSTATE cancer; MESSENGER RNA; CANCER treatment; GENE expression
- Publication
Cancer Cell International, 2018, Vol 18, p1
- ISSN
1475-2867
- Publication type
Article
- DOI
10.1186/s12935-018-0528-9