July 15 Clinical Cancer Research Highlights

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Selected Articles from the July 15, 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the July 15 issue of Clinical Cancer Research.

JunB Blocks Prostate Cancer Progression

Transient amplifying cells (TAC) are a subset of the basal cell population in the prostate from which cancers are thought to originate. Here, Konishi and colleagues isolated TAC clones from different regions in the prostate to study the molecular mechanism through which they become cancerous. They found that repeated transfection of JunB siRNA in prostatic TACs allowed the cells to escape senescence and promoted cellular invasion. Additionally, immunohistochemical analysis showed that JunB expression was very low in metastatic prostate cancers as well as in cancers with poor prognosis. These findings suggest that JunB functions to maintain cellular senescence and block malignant transformation in TACs. 

Activity of Curcumin in Pancreatic Cancer

Trastuzumab Resistance Mediated by t-DARPP

Trastuzumab is a monoclonal antibody against the ErbB2 receptor that is used in cancer therapy. Here, Belkhiri and colleagues identified a factor involved in trastuzumab resistance in breast cancer. They found high levels of the protein t-DARPP (a truncated form of dopamine- and cAMP-regulated phosphoprotein) in cell lines that were passaged in mice and developed trastuzumab resistance. The expression of t-DARPP increased the level and activity of AKT, a protein that is hyperactivated in trastuzumab-resistant breast cancers. Furthermore, t-DARPP expression blocked apoptosis and promoted cell survival. The investigators showed that knocking down t-DARPP in trastuzumab-resistant cells led to a significant decrease in their survival and sensitized them to trastuzumab. These results show that t-DARPP can mediate resistance to trastuzumab.

The BRIP1 (FANCJ/BACH1) gene, which encodes a DNA helicase, has been suggested as a low-penetrance breast cancer susceptibility gene. De Nicolo and colleagues performed a combination of genetic and functional studies to characterize a novel BRIP1 sequence alteration identified in a cohort of high-risk Italian families. They report BRIP1 loss of heterozygosity in tumor cells, show the absence of the mutant protein in immortalized lymphocytes, and show that the mutation impacts protein stability and disrupts protein interactions. This work provides an example of how performing a comprehensive analysis can distinguish disease-causing mutations from benign polymorphisms.