Disruption of Cell Cycle Machinery in Pancreatic Cancer

This chapter discusses the role of cell cycle machinery in initiation and progression of pancreatic cancer.Normal pancreatic cells-their types, organization, and functions-are first described to characterize the environment in which cellular transformation and tumor expansion occurs.The epidemiology and histology of pancreatic cancer is then briefly presented to emphasize the urgent need for earlier diagnosis and more effective treatments.Current efforts towards this goal are focused on understanding the disease at the molecular level, so the hallmarks of cancerous cells are discussed with respect to the progression model of pancreatic cancer development.Because the pancreas is composed of various cell types with different genetic backgrounds and regulatory systems, identifying the cell in which cancer originates is of utmost importance.Molecular mechanisms of normal proliferative control are then presented so that mechanisms by which they are disrupted can be appreciated.Particular attention is paid to how signaling transduction pathways and the cell cycle machinery cooperate to make cell fate decisions at the Restriction point.This analysis sets the stage for evaluating the role of cell cycle control mechanisms in transformation of the initiating cell in pancreatic cancer.The chapter concludes by arguing that genetic alterations associated with pancreatic cancer indicate disrupted cell cycle control mechanisms play a central role in disease development and progression. Pancreatic tissue organization and cellular functionEvaluating the role of cell cycle machinery in pancreatic cancer requires understanding the architecture and cellular organization of this dual-function gland.The pancreas is an approximately six inch long cylindrical organ in the abdomen, located between the stomach and the spine (Romer & Parsons, 1977).The endocrine component is composed of clusters of alpha, beta, and PP (pancreatic peptide) cell types that form structures called the islets of Langerhans (Jain & Lammert, 2009).These cells produce metabolic hormones involved in energy metabolism.Major cell types and their organization are summarized in Figure 1.www.intechopen.