Intratumor MAPK and PI3K signaling pathway heterogeneity in glioblastoma tissue correlates with CREB signaling and distinct target gene signatures.

Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumor heterogeneity. Heterogeneity arises due to the genetic and epigenetic variation of tumor cells in response to microenvironmental interactions and cytotoxic therapy. We explored specific signaling pathway activation in glioblastoma (GBM) by investigating the intratumor activation of the MAPK and PI3K pathways.

G2/M checkpoint gene expression in developing germ cells.

Cell cycle progression is prevented by signal transduction pathways known as checkpoints which are activated in response to replication interference and DNA damage. We cloned a G2/M cell cycle phase-related checkpoint gene from a neonatal mouse testis cDNA library which was identified as mouse claspin, a proposed adaptor protein for Chk1. As part of a study on germ cell differentiation we examined the expression of the checkpoint gene, Chk1, and claspin at 12.

Sorsby's fundus dystrophy: what does TIMP3 tell us about general mechanisms underlying macular degeneration?

INTRODUCTION: Mutations in tissue inhibitor of metalloproteinases-3 (TIMP3) gene result in the rare autosomal dominant disease Sorsby's fundus dystrophy (SFD), which shows striking similarities to age-related macular degeneration (ARMD). METHODS: Current research is reviewed and suggests that these mutations result in the accumulation of TIMP3 in Bruch's membrane resulting in decreased turnover of the extracellular matrix and consequent thickening of Bruch's membrane. DNA analysis of ARMD patients has failed to show any significant mutations in the coding-regions of TIMP3.

Expression of the ETS transcription factor ELF3 in the retinal pigment epithelium.

Purpose: The ETS family of transcription factors regulate several critical cellular functions. They have also been implicated in invertebrate ocular development. This work was undertaken to determine whether epithelium-specific ETS transcription factors are expressed in the retinal pigment epithelium and to investigate the possible role of these factors in retinal diseases such as age-related macular degeneration.