11,12 OED biomarkers and hallmarks www.selleckchem.com/products/MDV3100.html of cancer cells Oral carcinogenesis is a highly complex, multistep process involving accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), as well as the loss of proteins restraining cell proliferation (encoded by tumor suppressor genes).1 The molecules involved in these processes may therefore provide markers for the early detection of malignant transformation. Proteins investigated in OED by IHC belong to different family groups, including: growth factors, growth factor receptors, cell-cycle proteins, proliferation markers, cell-cycle inhibitors, apoptotic factors, angiogenic signals, and cell adhesion molecules, among others.
Figure 1 summarizes the pattern of protein expression and whether expression increases or decreases during oral carcinogenesis. Some proteins showed irregular expression patterns. Hanahan and Weinberg proposed six essential hallmarks of cancer cells that distinguish them from their normal counterparts.11,12 The hypothesized hallmarks include: self-sufficiency in growth signals, insensitivity to antigrowth signals, avoidance of apoptosis, resistance to cell senescence, development of new vascular supplies, and invasion and metastasis. Dysplastic epithelial cells are predisposed to develop these phenotypes as they progress toward cancer. Figure 2 summarizes how protein expression alterations identified in our review contribute to the acquisition of the essential hallmarks of oral cancer. The role of each marker in oral carcinogenesis is discussed below.
Figure 1 Pattern of protein expression during oral carcinogenesis. Figure 2 Schematic representation of contribution of protein alterations to the acquisition of the essential hallmarks of oral cancer. Proliferation without exogenous stimulation Normal cells require extracellular growth signals to proliferate, while cancer cells can grow without exogenous stimulation.11 This can occur through one or more of the mechanisms described below. Over-expression of extracellular growth signals Growth factors are extracellular signals that play an important role in the regulation of cell growth, proliferation, and differentiation by binding to their receptors on the cell membrane.11 Mitosis in a variety of mammalian epithelial cells is stimulated by epidermal growth factor.
Transforming growth factor-alpha (TGF-��) is an epidermal growth factor family protein.13 It has been found that the intensity Brefeldin_A of immunohistochemical expression of TGF-�� increases progressively as dysplasia advances from low grade to high grade, reaching its highest level in oral carcinoma.14 The level of expression of TGF-�� oncoprotein in dysplastic oral leukoplakia was clear when compared with adjacent histologically normal mucosa.