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Involvement of PI3K pathway in bladder cancer invasion

Institution: University of California, Davis
Investigator(s): Colleen Sweeney, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11KT-0236 Award: $224,984
Subject Area: Cancer
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Bladder cancer is the fifth most frequently diagnosed tumor in the United States, with more than 50,000 new cases and 11,000 deaths annually. Cigarette smoking is the premier etiological factor in bladder cancer. Strong links have been established between bladder cancer risk and the number of years an individual smokes cigarettes, as well as the number of cigarettes smoked per day. Moreover, smokers who quit after bladder cancer diagnosis fare better than patients who continue smoking. Hence, bladder cancer is one of the many diseases intimately associated with tobacco use. It is thought that many bladder tumors arise as a result of the body’s mechanism of extruding carcinogens as waste. Tobacco-derived carcinogens accumulate in the urine allowing for the continuous exposure of bladder epithelial cells to these agents. Carcinogens then induce mutations in genes that are responsible for the control of cellular growth properties. Mutations in genes involved in biochemical pathways that control cellular growth are thought to be responsible for the creation of new tumors and their progression to malignancy. The purpose of this proposal is to understand the contribution of a specific biochemical pathway to the progression of bladder cancer.

During their progression to malignancy cells from a primary tumor migrate through surrounding tissue as a first step in metastasis. This process, called invasion, is dependent of the ability of the tumor cell to degrade its surrounding tissue environment and migrate away from the primary tumor. The proposed studies focus on elucidating the participation of phosphatidylinositol 3-kinase (PI3K), an enzyme known to mediate cellular movement, in the invasive properties of bladder cancer cells. Using cultured human bladder tumor cell lines we will examine how the activation of PI3K and other components in its biochemical pathway influence invasion. Moreover, we will examine bladder cancer samples from patients to determine whether the activation of this pathway correlates with the progression of the disease, and hence could be used as a prognostic factor in the clinic.
Publications

The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion.
Periodical: British Journal of Urology International Index Medicus:
Authors: Wu X, Obata T, Khan Q, Highshaw RA, de Vere White R, Sweeney C ART
Yr: 2003 Vol: 93 Nbr: Abs: Pg: 143-150

The phosphatidylinositol-3 Kinase pathway regulates bladder cancer cell invasion
Periodical: British Journal of Urology International Index Medicus:
Authors: Wu, X, Obata, T, Khan Q, Highshaw RA, de Vere White R, Sweeney, C. ABS
Yr: 2004 Vol: 93 Nbr: Abs: Pg: 143-150