PDF Version for Printing
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 June 1 issue of Cancer Research
Linardic et al. Page 4490
The variable clinical presentation of rhabdomyosarcoma (RMS), a cancer with skeletal muscle characteristics, suggests that RMS may arise from many cell types. RMS has been difficult to model in mice; hence Linardic et al. genetically converted two primary human cell types in the skeletal muscle lineage to a tumorigenic state by disrupting pathways altered in RMS. While less differentiated cells gave rise to sarcomas of variable histology, committed myoblasts were converted to tumors resembling embryonal RMS, suggesting that myoblasts could give rise to RMS. The ability to genetically induce RMS in human cells should provide a model to systematically dissect the mechanisms underlying this malignancy.
Chang et al. Page 4496
Production of prostaglandin E2 (PGE2), a lipid mediator produced from cyclooxygenase-2 (COX-2), is increased in mammary cancer. Expression of COX-2 is correlated with poor survival and inhibitors of PGE2 synthesis reduce breast cancer incidence in humans. How PGE2 regulates cancer progression is poorly understood. Chang et al. used a COX-2 transgenic mouse model and examined the role of the EP2 receptor for PGE2. EP2 receptor is required for COX-2-induced mammary hyperplasia and regulates the expression of amphiregulin, a potent growth factor for mammary epithelial cells. EP2 receptor inhibitors may find utility in the control of breast cancer.
Hienonen et al. Page 4607
Defective DNA mismatch repair leads to microsatellite instability (MSI) and facilitates malignant transformation through increased mutation rates, for example, in coding microsatellite sequences. To date, putative MSI target genes have been proposed based on high mutation frequency, often without supporting functional evidence. Hienonen et al. report that high mutation frequencies–up to 70%–can be detected in short (9 bp) mononucleotide tracts in the absence of apparent selection pressure. Without functional evidence, therefore, the role of many previously proposed candidate MSI target genes in tumorigenesis should be interpreted with caution. These results call for extensive evaluation of mutation frequencies in neutral short repetitive sequences in MSI cancers.
Hu-Lieskovan et al. Page 4633
Ewing’s family tumors (EFTs) are consistently associated with a tumor-specific EWS-FLI1 translocation and a primitive neural phenotype. To explore whether fusion gene expression is responsible for the neural phenotype of EFTs, Hu-Lieskovan et al. investigated the effect of time-dependent ectopic EWS-FLI1 expression on the morphology, ultrastructure, immunophenotype, and transcriptome of RD embryonal rhabdomyosarcoma cells in vitro and in vivo. A trans-differentiation effect towards parasympathetic neuronal differentiation, similar to native EFTs, was observed. The authors conclude that EWS-FLI1 is responsible for the neuroectodermal differentiation of EFT, regardless of tissue of origin. These findings challenge traditional views of tumor histogenesis.
Tian et al. Page 4747
Germline mutations in the BRCA2 gene predispose women to familial breast and ovarian cancer. In addition to its role in DNA damage repair, BRCA2 also suppresses cell proliferation. In their current report, Tian et al. found that BRCA2 binds and stabilizes MAGE-D1 and that MAGE-D1 expression is required for BRCA2-mediated suppression of cell proliferation. These findings indicate that MAGE-D1 is a downstream target of BRCA2 and that BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Importantly, MAGE-D1 protein expression was reduced in 6 out of 16 breast carcinoma cell lines tested suggesting that suppression of MAGE-D1 expression may be involved in the tumorigenesis of breast cancers.