Mouse study focuses on inflammatory response produced in androgen ablation therapy

-- Jeff Muise

Monday, March 22, 2010 (Last Updated: 03/23/2010)

MONDAY, March 22 (HealthDay News) -- The progression of androgen-dependent prostate cancer (CaP) to castration-resistant CaP despite androgen ablation therapy is the result of an inflammatory response that enhances tumor cell survival, according to a letter in the March 11 issue of Nature.

Massimo Ammirante, Ph.D., of the University of California in San Diego, and colleagues investigated the role of the inflammation-responsive IκB kinase (IKK)-β protein and its target NF-κB in promoting the viability of malignant and inflammatory cells. The researchers conditionally deleted the Ikkβ gene in prostate epithelial cells of transgenic adenocarcinoma mouse prostate (TRAMP) mice, performed IKK-β ablation, and monitored them for subsequent CaP progression.

The researchers found that elimination of the IKK-β protein in the genetically modified prostate epithelial cells had no effect on progression of androgen-dependent CaP and development of castration-resistant CaP. The researchers concluded that CaP progression continued because inflammation led to infiltration of the shrinking androgen-dependent tumors with leukocytes, including B cells that produce lymphotoxins resulting in activated IKK-α and signal STAT3 transcription factor to enhance tumor cell survival.

"Castration-resistant CaP is a major complication that limits the success of androgen ablation therapy and is responsible for most mortality from prostate cancer. Castration-resistant CaP was studied mainly at the level of androgen-receptor function, the central player in this process. Our results suggest that an inflammatory response triggered by death of androgen-deprived primary cancer is another important contributor to emergence of castration-resistant CaP," the authors write.

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Specialties Oncology
Internal Medicine
Family Practice

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