RaLP, a new member of the Src homology and collagen family, regulates cell migration and tumor growth of metastatic melanomas.

The Src homology and collagen (Src) family of adaptor proteins comprises six Shc-like proteins encoded by three loci in mammals (Shc, Rai, and Sli). Shc-like proteins are tyrosine kinase substrates, which regulate diverse signaling pathways and cellular functions, including Ras and proliferation (p52/p46Shc), phosphatidylinositol 3-kinase and survival (p54Rai), and mitochondrial permeability transition and apoptosis (p66Shc). Here, we report the identification, cloning, and sequence characterization of a new member of the Shc family that we termed RaLP.

The polycomb group protein Suz12 is required for embryonic stem cell differentiation.

Polycomb group (PcG) proteins form multiprotein complexes, called Polycomb repressive complexes (PRCs). PRC2 contains the PcG proteins EZH2, SUZ12, and EED and represses transcription through methylation of lysine (K) 27 of histone H3 (H3). Suz12 is essential for PRC2 activity and its inactivation results in early lethality of mouse embryos.

Circulating endothelial cells as a novel marker of angiogenesis.

Measurement of tumor angiogenesis to predict and/or to assess the efficacy of antiangiogenic therapies is mainly based on the evaluation of microvessel density (MVD). We developed a novel flow cytometry procedure to measure circulating endothelial cells (CECs) and circulating endothelial cells progenitors (CECPs) in either preclinical and clinical studies. Preclinical studies were performed on an animal model of human lymphoma.

Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors.

Purpose: We investigated the effect of endostatin on differentiation, mobilization, and clonogenic potential of circulating endothelial cell (EC) progenitors, and whether the effect of endostatin was improved by continuous infusion (CI) versus bolus administration.

Experimental Design: Four-color flow cytometry and clonogenic EC cultures were used to study EC progenitors in tumor-free mice, tumor-bearing immunodeficient mice, and immunodeficient mice xenotransplanted with human bone marrow (BM) cells.

Results: Endostatin significantly reduced the number of circulating EC progenitors in tumor-free BALB/c mice.

PML-RAR induces promyelocytic leukemias with high efficiency following retroviral gene transfer into purified murine hematopoietic progenitors.

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations resulting in fusion proteins of the retinoic acid receptor (RAR). Here, we report a novel murine model system for APL, based on the transduction of purified murine hematopoietic progenitors (lin(-)) using high-titer retroviral vectors encoding promyelocytic leukemia-RAR (PML-RAR), and the green fluorescent protein (GFP) as a marker. PML-RAR-expressing lin(-) cells were impaired in their ability to undergo terminal myeloid differentiation and showed increased proliferative potential in vitro.

In vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue.

Objective: We studied the in vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue collected from adults with head and neck cancer.

Materials And Methods: Adherent muscle cells were cultured in F12 medium with 10% fetal bovine serum and transplanted into immunodeficient mice.

Results: On day 12 we obtained a median of 500,000 adherent cells per gram muscle sample.

Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development.

We report here the characterization of a mutant mouse line with a specific gene trap event in the Mdm4 locus. Absence of Mdm4 expression results in embryonic lethality (10.5 days postcoitum [dpc]), which was rescued by transferring the Mdm4 mutation into a Trp53-null background.