April 1 Cancer Research Highlights

Selected Articles from the April 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 April 1 issue of Cancer Research.

Pancreatic Stellate Cells and Cancer Cells: Partners in Crime

Vonlaufen et al.

Page 2085

Until recently, the role of epithelial-stromal interactions in the pathogenesis of pancreatic cancer has received relatively little attention. Using novel in vivo and in vitro approaches to study human pancreatic cancer, Vonlaufen and colleagues provide compelling evidence of a significant bidirectional interaction between cancer cells and stellate cells, a stromal cell type known to produce the pathologically important desmoplastic/stromal reaction in pancreatic cancer. The authors’ findings suggest that pancreatic cancer cells actively recruit stromal cells to establish an environment that promotes cancer progression. The findings are likely to be applicable to other cancers that have prominent stromal components, such as breast and prostate cancers, and characterizing the molecular pathways involved may be useful in the development of targeted therapies.

Origins and Prevalence of the American Founder Mutation of MSH2

Clendenning et al.

Page 2145

The American Founder Mutation (AFM) in the DNA repair gene MSH2 leads to an inherited susceptibility to cancer. In their study, Clendenning and colleagues report 32 new families who carry the AFM, a chromosomal deletion of exons 1 to 6 in MSH2 originally described in nine Lynch Syndrome families in the United States. Genealogical studies connect 27 of the 41 AFM families into seven extended pedigrees dating back to the 18th century. A common disease haplotype of between 0.6 and 2.3 Mb in all probands analyzed offers evidence of a common ancestor among these families in whom the AFM arose ~500 years ago. A major implication of this study is that the AFM may be much more frequent in the United States than previously predicted.

Lkb1 Deficiency Causes Prostate Neoplasia

Pearson et al.

Page 2223

Mutation of the cell polarity gene LKB1 is the key molecular event underlying Peutz-Jegher’s syndrome, a condition characterized by multiple malignancies, including those of the reproductive system. Using a mouse model system that permits this gene to be deleted in a conditional manner, Pearson and colleagues addressed the role of Lkb1 in prostate neoplasia. Lkb1 deletion reduced longevity and predisposed to prostate intraepithelial neoplasia (PIN) within 2 to 4 months. PIN foci overexpressed nuclear β-catenin and downstream Wnt targets along with activation of the Akt pathway. The findings of this study prompt further investigations of the potential role of Lkb1 inactivation in human prostate formation or progression and prostate neoplasia, suggesting a similar association in humans.

Hepsin-Targeted Imaging of Prostate Cancer

Kelly et al.

Page 2286

Kelly et al. Early detection of prostate cancer is key to designing effective treatment strategies. Hepsin is specifically up-regulated in prostate cancer with little expression in benign prostatic hyperplasia or normal tissues, making it a potentially useful tool in developing imaging agents for prostate cancer. To explore this potential, Kelly and colleagues developed a reagent that binds hepsin with high affinity and specificity and used it to detect 4.6-mm diameter prostate tumors. The findings of this study suggest that hepsin-targeted agents might be helpful in a variety of settings, including biopsy targeting, the delineation of nonlocalized disease, and the identification of disease recurrence posttherapy.

Statins Are Novel HDAC Inhibitors

Lin et al.

Page 2375
Lin et al.

Statins are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase that are widely used to control hypercholesterolemia. Lin and colleagues now report that statins can inhibit histone deacetylase (HDAC) activity, increase the levels of acetylated histone-H3, and increase the expression of the cell cycle kinase inhibitor p21WAF1. Computational modeling was employed to corroborate a model in which the common carboxylic acid moiety of statins interacts directly with the catalytic site of HDAC2. Mechanistic investigations identified the transcription factor Sp1 and the coactivator CBP as critical elements in mediating the ability of statins to stimulate the p21WAF1 promoter in cancer cells. The findings of this study suggest that statins exert HDAC inhibitory activities that may help prevent cancer.

April 1 Cancer Research Highlights

Selected Articles from the April 1, 2008 Issue

Pancreatic Stellate Cells and Cancer Cells: Partners in Crime

Origins and Prevalence of the American Founder Mutation of MSH2

Lkb1 Deficiency Causes Prostate Neoplasia

Hepsin-Targeted Imaging of Prostate Cancer

Statins Are Novel HDAC Inhibitors

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