April 15 Highlights: CR

December 15 Cancer Research Highlights

Selected Articles from the December 15, 2007 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 December 15 issue of Cancer Research.

Oncogenic Pathways Specific to Basal and Luminal Breast Cancer Subtypes

Adélaïde et al.

Page 11565

Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. Adélaïde and colleagues have reported a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. The results support the existence of specific oncogenic pathways in basal and luminal breast cancers involving several potential oncogenes and tumor suppressor genes. HORMAD1 and ZNF703 were the most significant distinguishing genes defining basal and luminal potential oncogenes, respectively. Among chromosome 10p candidate oncogenes associated with the basal subtype, the authors also validated the CDC123 protein as a basal type marker.

Flat Colorectal Cancers Skip Polypoid Stage

Uronis et al.

Page 11594

The etiology of flat (non-polypoid) colorectal cancers, which are difficult to detect by routine colonoscopy, has been the subject of significant controversy. Supporters of the adenoma-carcinoma sequence posit that flat carcinomas originate through an adenoma intermediate while others have asserted that these cancers form de novo, lacking any adenomatous precursor. Uronis and co-investigators used serial colonoscopy and histology to follow the development of flat colorectal cancers from normal epithelia in mice. Their results show that flat colorectal cancers arise through a flat adenomatous intermediate and progress to invasive cancer without going through a demonstrable polypoid stage. Thus, not all colorectal cancers use a common pathway for tumor progression.

New Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia Created

Omidvar et al.

Page 11657

Myelodysplastic syndromes (MDS) are clonal stem cell hematological disorders that evolve to acute myeloid leukemia (AML) and thus model multistep leukemogenesis. Activating RAS mutations and overexpression of BCL-2 are prognostic features of MDS/AML transformation. Using NRASD12 and BCL-2, Omidvar and colleagues created two distinct models of MDS and AML, where human BCL-2 is conditionally or constitutively expressed. This represents the first in vivo progression model of MDS/AML dependent on the formation of a BCL-2:RAS-GTP complex. The colocalization of BCL-2 and RAS in the bone marrow of MDS/AML patients suggests that targeting either oncogene may be a good therapeutic strategy to pursue.

Novel Noncatalytic Role for Caspase-8 in Neuroblastoma Cells

Finlay and Vuori

Page 11704

Neuroblastomas are extremely aggressive, though heterogeneous, cancers with a poor prognosis upon metastasis. Previous evidence has suggested a correlation between silencing of caspase-8 with MYCN amplification in neuroblastoma; however, a prognostic effect of this silencing has been disputed. Finlay and Vuori report previously undescribed roles for caspase-8 in the modulation of cell adhesion and subsequent activation of the Erk signaling pathway apparently independent of its cleavage activity. The association of caspase-8 and Src, coupled with downstream signaling events, may help explain why a potential tumor suppressor such as caspase-8 is rarely absent in cancers.

Dietary Energy Restriction Exerts No Effect on the Warburg Pattern in Energy Metabolism

Zhu et al.

Page 12018
Zhu et al.

The objective of this study was to determine whether dietary energy restriction (DER) affects the pattern of gene expression in three interrelated energy metabolism pathways: glycolysis, gluconeogenesis, and the citric acid cycle. Using high-resolution arrays, the patterns of expression observed by Zhu and colleagues were most consistent with the Warburg effect. These findings imply that efforts to target the Warburg effect for cancer prevention are mechanistically distinct from those modulated by DER and provide a rationale for the combination of approaches that target basic defects in energy metabolism and energy-sensing pathways for the prevention of breast cancer.

December 15 Cancer Research Highlights

Selected Articles from the December 15, 2007 Issue

Oncogenic Pathways Specific to Basal and Luminal Breast Cancer Subtypes

Flat Colorectal Cancers Skip Polypoid Stage

New Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia Created

Novel Noncatalytic Role for Caspase-8 in Neuroblastoma Cells

Dietary Energy Restriction Exerts No Effect on the Warburg Pattern in Energy Metabolism

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