April 1 Cancer Research Highlights

PDF Version for Printing

Selected Articles from the April 1, 2006 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the April 1 issue of Cancer Research.

Met Amplification in Mice Suggests Recurrent Secondary Genetic Events

Recurrent genomic abnormalities involved in either initiation or progression of cancer provide an opportunity to identify genes that may be essential to tumorigenesis. In a genomic analysis of mouse mammary tumors initiated by inactivation of Brca1 and Trp53, Smolen et al. found that 11/15 (73%) have high-level amplification of the gene encoding the growth factor receptor Met. However, MET amplification was not observed in human familial or sporadic breast tumors. Nonetheless, their finding that Met amplification constitutes a frequent secondary genetic event in Brca1/Trp53 mouse tumors raises the possibility that similar genomic screens might identify an equivalent recurrent genetic lesion driving cellular proliferation in human BRCA1-associated breast cancers.

Paradoxical Estrogen Downplays Endothelial Id-1

2-Methoxyestradiol (2ME₂) has apparent paradoxical effects on tumor growth depending upon the stage of administration in a transgenic model of breast cancer. While 2ME₂ reduces growth of palpable tumors through increased apoptosis, it results in large, cystic tumor formation when administered at the earliest stages of lesion formation, consistent with impaired angiogenesis. Huh et al. report that 2ME₂ inhibits expression of Id-1, an important transcription factor for endothelial cell function, providing another antitumor mechanism of action of 2ME₂. Inhibition of angiogenesis at early stages may not be sufficient to prevent tumor growth, which likely requires combination therapy with a cytotoxic agent.

Cells Use Ruffles To Dip into EGFR Numbers

The epidermal growth factor receptor (EGFR) is amplified and/or mutated in many cancer types. It is well established that ligand-bound EGFR is internalized through clathrin-coated pits. In this study, Orth et al. have identified cellular dorsal ruffles or “waves” as transient organelles that form in response to EGF and actively sequester and internalize up to 50% of the total internalized EGFR. This remarkably rapid and selective sequestration of activated EGFRs away from other surface receptors occurs without the use of conventional endocytic coat proteins, including clathrin, and is likely to play a major role in how receptor-mediated processes may affect receptor down-regulation, cell growth, motility, and metastasis.

Embryonic Stem Cells Generate Tumor Cell Microenvironment Sanctuary

To further improve the understanding of the role that tumor-stromal interactions play in tumorigenesis and anticancer therapy, Tzukerman et al. have used human embryonic stem cells to create a cellular microenvironment that provides a supportive sanctuary, promoting tumor cell invasion as well as neovascularization of human cellular origin for a variety of human tumor cell types. Epidermoid carcinoma–derived tumor cells growing within this sanctuary resisted full eradication by anticancer immunotherapy. These findings provide a proof of principle for the potential development of this approach as a novel preclinical platform for investigating tumorigenesis properties and for predicting the efficacy of anticancer therapy.

Fruits Outperform Vegetables in Protecting against Colorectal Adenomas

Consumption of fruits and vegetables may confer protection from colorectal adenomas, but the limited observational and interventional evidence is inconclusive. Michels et al. examine this association in the Nurses’ Health Study using data from 34,467 women who had undergone colonoscopy or sigmoidoscopy. Between 1980 and 1998, 1,720 prevalent cases of adenoma of the distal colon and rectum were diagnosed. Frequent consumption of fruit was inversely related to the risk of being diagnosed with polyps, whereas little association was found for vegetable consumption. Frequent consumption of fruit may reduce the risk of colorectal adenomas.