American Association for Cancer Research

June 1 Cancer Research Highlights

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


p38δ Is Required for Skin Carcinogenesis

Schindler et al.

Page 4648

The mammalian p38 mitogen-activated protein kinase family includes p38α, p38β, p38γ, and p38δ isoforms. The in vivo roles of individual p38 kinases in skin tumorigenesis have not been elucidated. Using p38δ knockout mice, Schindler and colleagues show that p38δ deficiency results in a significant protection against skin tumor development in a chemical skin carcinogenesis model. Mice lacking p38δ exhibit delayed onset of tumors, as well as reduced incidence, multiplicity, and size of tumors, compared with wild-type mice. The results suggest that a reduced susceptibility of p38δ knockout mice to skin carcinogenesis can, in part, be attributed to an aberrant proliferative response during tumor promotion. These findings demonstrate the importance of p38δ in promoting skin tumorigenesis and suggest that targeting p38d may have therapeutic implications for skin cancer. 
 

Embelin Inhibits Colon Carcinogenesis in Mice

Dai et al.

Page 4776

Embelin, an antagonist against X-linked inhibitor of apoptosis protein, possesses multiple biological activities, including an anticancer effect. However, the mechanisms by which embelin inhibits tumorigenesis remain largely unknown. Recent studies have indicated that PPARγ plays a crucial role in colon carcinogenesis. Dai and colleagues report that embelin is able to inhibit growth and induce apoptosis in colon cancer cells in vitro. In addition, embelin suppresses colon carcinogenesis induced by the carcinogen DMH in a mouse model. These effects are partially dependent on the presence of functional PPARγ. These results demonstrate for the first time that functional PPARγ is required for embelin to exert its antitumor effect in colon cancer, suggesting that embelin may be a potential chemopreventive agent against colon cancer.


GLI1 Induces Mammary Tumors

Fiaschi et al.

Page 4810

Aberrant Hedgehog (Hh) signaling is implicated in the development and maintenance of breast cancer, but conclusive evidence that activated Hh signaling can cause mammary tumor formation is lacking. Fiaschi and colleagues now show that transgenic expression of human GLI1, a Hh effector protein, is sufficient to induce expansion of a cell population expressing progenitor cell markers and to initiate tumor formation in the mouse mammary gland. GLI1-induced tumors display varying differentiation patterns and hallmarks of an aggressive growth pattern. The data provide support for a role of Hh/GLI signaling in breast cancer development and suggest that targeting Hh signaling may represent a new therapeutic opportunity.


Colitis and Systemic Genotoxicity

Westbrook et al.

Page 4827

Westbrook et al.Inflammatory bowel disease increases risk of colorectal cancer; however, mechanisms exploring the process from inflammation to dysplasia remain elusive. Westbrook and colleagues analyzed peripheral blood for markers of DNA damage in mice with chemically-induced colitis and in mice that spontaneously develop immune colitis, with differing levels of clinical severity. Genotoxicity in the form of DNA single- and double-strand breaks, oxidative base damage, and micronuclei formation was observed away from the site of inflammation in peripheral leukocytes and erythroblasts, correlating with clinical severity of inflammation. Systemic genotoxicity may be a biologically relevant and sensitive biomarker of one process contributing to inflammation-associated carcinogenesis.  


miRNA Expression in Bladder Cancer

Dyrskjøt et al.

Page 4851

Dyrskjøt et al.miRNAs have been shown to be involved in cancer development and progression. Dyrskjøt and colleagues identified several differentially expressed miRNAs between normal urothelium and cancer, and between the different disease stages. Furthermore, miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*) were identified. Interestingly, miR-129 exerts significant growth inhibition and induces cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines. These findings indicate that several miRNAs are differentially regulated in bladder cancer, and may form a basis for clinical development of new biomarkers for bladder cancer. 


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