January 1 Cancer Research Highlights

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Selected Articles from the January 1, 2009 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 January 1 issue of Cancer Research.

Ligand-Independent AR Variants in Prostate Cancer

Impaired Bub1 Function In vivo Leads to Aneuploidy, Tumorigenesis

Spindle assembly checkpoint (SAC) is a major guardian of mitotic fidelity. Bub1 is a serine/threonine kinase that localizes to kinetochores during mitosis and mediates efficient kinetochore localization of other SAC components. Schliekelman and colleagues developed a conditional Bub1 mutation in mice, resulting in a severe reduction in Bub1 levels. In mouse embryonic fibroblasts (MEFs), Bub1 mutation causes high rates of chromosome missegregation and aneuploidy accompanied by growth defects and senescence although the spindle checkpoint is functional. BubR1 kinetochore localization is markedly reduced in Bub1 mutant MEFs, suggesting that Bub1 plays a key role in a BubR1-dependent tension-sensitive SAC response. These findings indicate that Bub1 is critical for proper progression through mitosis and that defects in Bub1 signaling cause severe defects ranging from early lethality to tumorigenesis.

Neuropeptide Model for Androgen-Insensitive Prostate Cancer

While pleural mesothelioma is caused by asbestos exposure, as-bestos is a relatively weak mutagenic carcinogen. Christensen and colleagues therefore investigated the potential of asbestos to act primarily as an epigenetic carcinogen by measuring DNA methylation in hundreds of cancer-related genes in mesothelioma and pleural tissues. Methylation profiles generated from unsupervised clustering and supervised random forests classification indicate that epigenetic alterations are extraordinarily common in mesothelioma and significantly discriminate the malignant phenotype from normal pleura. Further, the authors characterized specific asbestos-related methylation alterations, confirming the association between high lung tissue asbestos burden and poor prognosis, and show that methylation profiles are independent predictors of prognosis.  

Protumorigenic Function of Keratinocyte CXCR2