Differential mRNA expression of the main apoptotic proteins in normal and malignant cells and its relation to in

Andrea Vazanova1,2, Jana Jurecekova1,3, Tomas Balharek4

  • 11Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin (JFM), Comenius University in Bratislava (CU), Mala Hora 4D, 03601 Martin, Slovak Republic.

Abstract

Insights

Investigating apoptotic gene expression in cancer patients revealed elevated p53 and BAX mRNA in leukemia. High Bcl-2 levels appear to block apoptosis, suggesting personalized combination therapy for improved cancer treatment outcomes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Apoptosis is crucial for multicellular organism development and homeostasis.
  • Deregulation of apoptosis is linked to severe diseases, including cancer.
  • Oncogenic mutations can disrupt apoptosis, driving tumor initiation, progression, and metastasis.

Purpose of the Study:

  • To investigate the expression of apoptotic genes in cancer patients.
  • To explore the relationship between gene expression and drug resistance.
  • To assess the impact of specific gene levels on chemoresistance.

Main Methods:

  • Analysis of 102 samples from leukemia (n=60) and solid tumor (n=42) patients.
  • Quantitative RT-PCR to measure mRNA expression levels of p53, BAX, Bcl-2, and Bcl-XL.
  • In vitro chemoresistance evaluation of leukemic cells using the MTT assay.

Main Results:

  • Statistically significant increase in p53, BAX, Bcl-2, and Bcl-XL mRNA in leukemia samples compared to healthy volunteers.
  • No significant difference in mRNA levels observed among solid tumor samples.
  • Positive correlation between p53 and BAX mRNA in both patient groups; highest Bcl-2/BAX ratio in solid tumors.

Conclusions:

  • Elevated p53 and BAX mRNA may signal genomic DNA integrity changes during malignant transformation.
  • p53 likely regulates BAX, but high Bcl-2 levels may inhibit p53-mediated apoptosis.
  • Differential apoptosis resistance mechanisms necessitate personalized combination therapies for oncological patients.

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