Review Article: The Role of Ras Superfamily Proteins in Bladder Cancer Progression

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Abstract
The prognosis of patients with bladder cancer is strongly dependent on whether the lesion is superficial or invasive at initial presentation. In addition, a significant fraction of patients presenting with superficial disease have invasive tumor during followup. Understanding how superficial bladder cancer progresses to invasive forms of the disease is of paramount importance for early diagnosis and successful treatment. Molecular mechanisms underlying bladder cancer progression are being elucidated. We reviewed the roles that members of the Ras superfamily of monomeric G proteins, an important class of cellular regulator, have in bladder cancer and its progression. We performed MEDLINE searches focusing on members of the Ras superfamily of monomeric G proteins and their involvement in transitional cell carcinoma, which is the most common form of bladder cancer. General involvement in cancer of key superfamily members, focusing on mechanisms and downstream pathways, was also reviewed through MEDLINE and manual bibliographic searches. With more than 100 members in humans the Ras superfamily is a diverse group of monomeric G proteins. These proteins regulate many cellular processes, such as cell cycle progression, actin cytoskeletal dynamics and membrane traffic. Members of the Ras and Rho family are also known to be involved in human cancer through mutation, over expression and dysregulation. In this review we focus on bladder cancer. In particular we focus on how H-Ras, RalA/B and RhoGDI2, a regulator of Rho family members, participate in bladder cancer progression and how their participation may be related to other molecules associated with bladder cancer progression, such as epidermal growth factor receptor, p53 and PTEN (phosphatase and tensin homologue deleted on chromosome 10). The findings discussed offer the hopeful possibility that signaling pathways mediated by Ras superfamily members may offer new opportunities for diagnostic and therapeutic interventions in bladder cancer.