Differential expression of CDC25 phosphatases splice variants in human breast cancer cells

Background: CDC25 phosphatases control cell cycle progression by activating cyclin dependent kinases. The three CDC25 isoforms encoding genes are submitted to alternative splicing events which generate at least two variants for CDC25A and five for both CDC25B and CDC25C. An over-expression of CDC25 was reported in several types of cancer, including breast cancer, and is often associated with a poor prognosis. Nevertheless, most of the previous studies did not address the expression of CDC25 splice variants. Here, we evaluated CDC25 spliced transcripts expression in anti-cancerous drug-sensitive and resistant breast cancer cell lines in order to identify potential breast cancer biomarkers. Methods: CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original real-time RT-PCR assay. Results: CDC25 spliced transcripts are differentially expres-sed in the breast cancer cell lines studied. An up-regulation of CDC25A2 variant and an increase of the CDC25C5/C1 ratio are associated to the multidrug-resistance in VCREMS and DOXOR breast cancer cells, compared to their sensitive counterpart cell line MCF-7. Additionally, CDC25B2 tran-script is exclusively over-expressed in VCREMS resistant cells and could therefore be involved in the development of certain type of drug resistance. Conclusions: CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.

Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

Análisis de la adecuación de libros de texto de E. Primaria a la enseñanza a estudiantes de altas capacidades matemáticas

Un problema al que se enfrentan los profesores de matemáticas de Enseñanza Primaria es la necesidad de hacer adaptaciones en sus programaciones para ofrecer una educación adecuada a sus alumnos de altas capacidades matemáticas. Las editoriales de libros de texto de matemáticas de estos niveles educativos ofrecen diversas soluciones que, usualmente, consisten en incluir, en el libro del alumno, algunos problemas más difíciles y, en la documentación del profesor, una propuesta de problemas de ampliación. Una cuestión que se plantea al analizar un libro de texto de matemáticas es valorar cómo de útil puede ser el material proporcionado por la editorial (libro de texto y materiales complementarios) para un profesor que necesita una programación específica para sus alumnos de altas capacidades matemáticas. En este artículo proponemos diversas variables con las que valorar el grado de adecuación a estudiantes de altas capacidades matemáticas de los documentos proporcionados a los profesores por las editoriales. Después ponemos en práctica esta propuesta analizando el tema dedicado a los cuadriláteros en 4º curso de Enseñanza Primaria de una editorial de amplia difusión en España. Las conclusiones globales son que los materiales del profesor analizados prestan poca atención a los estudiantes de altas capacidades matemáticas y que la metodología de análisis que hemos empleado permite identificar direcciones para plantear actividades interesantes para estos estudiantes.