Generation and characterization of EphA1 receptor tyrosine kinase reporter knockout mice.

Eph receptor tyrosine kinases (RTKs) are a highly conserved family of signaling proteins with functions in cellular migration, adhesion, apoptosis, and proliferation during both adult and embryonic life. Here, we describe a knock-in mouse in which EphA1 expression is disrupted via the insertion of an internal ribosome entry site (IRES)-human placental alkaline phosphatase (ALPP) reporter cassette into exon II of the EphA1 gene. This was shown to successfully knockout expression of endogenous EphA1 and enforce expression of the ALPP reporter by the EphA1 promoter.

Epithelial morphogenesis and intestinal cancer: new insights in signaling mechanisms.

In this review, the major signal transduction pathways that have been shown to play an important role in intestinal homeostasis are highlighted. Each of them, the Wnt, Notch, Hedgehog, and Bone Morphogenetic Protein, as well as growth-factor regulated Receptor Tyrosine Kinases are depicted with a special emphasis through their involvement in stem cell maintenance and their role in intestinal tumorigenesis. Finally, we discuss recent data on the final steps of tumor progression, notably the formation of distant metastases.

Maxillary transverse discrepancies and potentially impacted maxillary canines in mixed-dentition patients.

Objective: To investigate the correlation between maxillary transverse discrepancy and the occurrence of impacted canines in patients during the mixed-dentition stage.

Materials And Methods: Panoramic radiographs and dental casts were evaluated of randomly selected patients in the mixed dentition. The experimental group consisted of 84 orthodontic patients with a maxillary transverse discrepancy.

Expression analysis of the Epha1 receptor tyrosine kinase and its high-affinity ligands Efna1 and Efna3 during early mouse development.

Interaction of Eph receptor tyrosine kinases with their membrane bound ephrin ligands initiates bidirectional signaling events that regulate cell migratory and adhesive behavior. Whole-mount in situ hybridization revealed overlapping expression of the Epha1 receptor and its high-affinity ligands ephrin A1 (Efna1) and ephrin A3 (Efna3) in the primitive streak and the posterior paraxial mesoderm during early mouse development. These results show complex and dynamic expression for all three genes with expression domains that are successively complementary, overlapping, and divergent.

Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53.

More than 50% of human cancers contain p53 gene mutations and as a result accumulate altered forms of the full-length p53 protein. Although certain tumor types expressing mutant p53 protein have a poor prognostic process, the precise role of mutant p53 protein in highly malignant tumor cells is not well defined. Some p53 mutants, but not wild-type p53, are shown here to interact with Daxx, a Fas-binding protein that activates stress-inducible kinase pathways.

A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa.