Abnormal Expression of Induces S-phase Arrest and Mitotic Catastrophe in Human T-lymphocyte Leukemia

Background: Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death.

Methods: This study investigated the effect of expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Ras) or oncogenic mutant in codon 12 exon 1 (Ras) versions of gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The , ANOVA, and Scheffe tests were used for statistical analysis.

Results: Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, <0.0005) or mutated (81.79%, <0.0001) genes. Although similar effects for both versions of were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe.

Conclusion: Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.