CENTRO DE INVESTIGACIONES BIOLÓGICAS
Department of Cell and Developmental Biology
Molecular Biology of Chromosomes
Most Recent Achievements

Background

     Tumor processes share two main characteristics: control loss of cell division and block of cell differentiation. In some cases these two processes may revert, in which case the regulation of proliferation and differentiation is re-established. One of the main objectives of this project is the study of the molecular basis that leads tumor cells to regain control of cell differentiation. Murine erythroleukemia (MEL) cells, also known as Friend cells, are our model system. These cells derive from proerythroblasts that were immortalized with the Friend viral complex. When MEL cells are treated with HMBA they are able to re-enter their original differentiation program. This process leads MEL cells to develop the erythroid phenotype (Figure 1).

Figure 1. MEL cells can be induced to re-enter the cell differentiation program that leads them to acquire the erythroid phenotype. Differentiated cells are detected by the Benzidine assay. Benzidine reacts with hemoglobin leading to a dark blue stain (upper panel). After 4-5 days of treatment with HMBA, most of the cells are already differentiated and produce great amounts of hemoglobin (lower panel).

     The mechanism by which some chemical agents induce MEL cell differentiation is still unknown. It was clearly shown, however, that throughout the process, even at very early stages where no erythroid phenotype is yet detected, important changes occur in the expression of several genes. The possibility that these changes could be crucial to regain cell differentiation and the erythroid phenotype, led us to use differential hybridization and/or substraction techniques to test cDNA libraries that were made with mRNAs from MEL cells that were treated with HMBA. Significant changes were detected in the expression of several genes, such as the replication histone variants H3.3A (López Alañón et al, 1997; López Fernández et al, 1997), H3.3B (Krimer et al 1993) and H2A.Z, the 5S ribosomal protein (Vanegas et al, 1997), the Ran GTPase (Vanegas et al, 2003) and a triosophosphate isomerase, among others.