American Association for Cancer Research

March 1 Cancer Research Highlights

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Selected Articles from the March 1, 2008 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 March 1 issue of Cancer Research.


Chromosomal Breakpoints Cluster at Copy Number Variants

Camps et al.

Page 1284

Genomic aberrations on chromosome 8 are common in colon cancer and are associated with lymph node and distant metastases, and with disease susceptibility. Camps and colleagues generated a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones, confirming the dominant role of this chromosome. The authors observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants. 
 

Dlx5 Cooperates with Akt2 to Promote Lymphomagenesis

Tan et al.

Page 1296

Tan et al.The oncogene v-akt was isolated from a retrovirus that induced murine thymic lymphomas. Transgenic mice expressing a constitutively activated form of the cellular homolog Akt2, specifically in immature T cells, develop spontaneous thymic lymphomas. Tan and colleagues hypothesized that tumors from these mice might exhibit oncogenic chromosomal rearrangements that cooperate with activated Akt2 in lymphomagenesis. Experimental overexpression of Dlx5 in mammalian cells resulted in enhanced cell proliferation and increased colony formation, and clonogenic assays revealed cooperativity when both Dlx5 and activated Akt2 were coexpressed. These findings suggest that Dlx5 can act as an oncogene by cooperating with Akt2 to promote lymphomagenesis. 


New Breast Epithelial Model Elucidates Invasion Pathways

Riziki et al.

Page 1378

Riziki et al.In breast cancer, the transition from preinvasive to invasive phenotype is the defining criterion for malignancy. Rizki and colleagues describe a new human breast epithelial cell model that recapitulates malignant transformation of aggressive squamous and basal-like subtype breast tumors. The demonstrated utility of this model in discovering invasion pathways provides an opportunity to find new genes as potential markers of breast precancer recurrence and progression. 


Hebbard et al.The cell adhesion molecule and adiponectin-binding protein T-cadherin is lost from the carcinogenic mammary epithelium and dramatically up-regulated in the tumor vasculature. Deficiency in mice restricts tumor growth in the MMTV-PyV-mT breast cancer model but also leads to a more invasive and metastatic tumor cell behavior. Hebbard and colleagues demonstrated that T-cadherin regulates tumor angiogenesis and its absence ablates the association of the adipocyte-derived, circulating metabolic hormone adiponectin with the tumor vasculature. This work links adiponectin with a proangiogenic role for T-cadherin, and provides a cautionary example that restricted angiogenesis might result in more aggressive disease. 


Broccoli Sprouts Inhibit Bladder Carcinogenesis

Munday et al.

Page 1593

Isothiocyanates are a well-known class of chemopreventive agents. Broccoli sprouts are a rich source of several isothiocyanates. To evaluate the inhibitory activity of broccoli sprouts against bladder cancer, Munday and colleagues fed a freeze-dried extract of broccoli sprouts to rats exposed to a nitrosamine carcinogen and found that the extract markedly inhibited bladder cancer development. The extract also significantly elevated several anticarcino­genic enzymes in the bladder. The isothiocyanates appear to be selectively delivered through urinary excretion to the bladder epithelium, the principal site of bladder cancer development. Thus, the extract is a highly promising substance for bladder cancer prevention. 


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