July 26, 2012

On the hunt for bladder cancer factors

A protein linked to aggressive bladder cancers could point to new strategies for treatment or prevention.

(Wellcome Images)

Nearly 15,000 people in the United States die each year from metastatic bladder cancer. Signaling pathways that cause bladder tumor recurrence and spread are not clear.

David DeGraff, Ph.D., a post-doctoral fellow in Urologic Surgery, and a multi-disciplinary team of colleagues including basic scientists, clinical pathologists and urologic surgeons, examined the role of the transcription factor FOXA1 in bladder cancer. FOXA1 controls gene expression and participates in the differentiation (maturation) of cells lining the bladder during development – a role that might be perturbed in tumor progression. In human bladder cancer specimens, the researchers found that decreased FOXA1 expression associated with increasing tumor stage and grade. The team also used a novel in vivo tissue recombination system to demonstrate that reduced FOXA1 expression enhanced tumor proliferation.

The findings, reported May 10 in PLoS ONE, link loss of FOXA1 expression to aggressive bladder cancers and suggest that this protein – and the gene expression network it regulates – plays a role in the malignant progression of bladder cancer.

This research was supported in part by grants from the National Institutes of Health (CA143971, DK055748, RR024975, CA113452), by a Merit Review Award from the Veterans Administration and by a Postdoctoral Fellowship Award to David DeGraff from the American Cancer Society Great Lakes Division.