Signaling during mouse skin tumor progression

Abstract

During malignant progression tumor cells acquire the ability to invade surrounding tissues and metastasize to distant organs. In epithelial tumors, malignancy correlates with loss of the epithelial phenotype and gain of fibroblastic characteristics. The mouse skin system has been extensively used to study molecular and cellular events leading to initiation, promotion and progression of tumorigenesis. In the mouse skin carcinogenesis model, initiated keratinocytes containing a carcinogen-induced H-Ras oncogene mutation give rise to benign papillomas, some of which progress to squamous cell carcinomas. Late stages of carcinogenesis are associated with the development of highly invasive and metastatic spindle carcinomas. In vitro and in vivo studies using this and other epithelial cell systems have shown that TGF-b1 induces the squamous-spindle carcinoma transition, and that an activated H-Ras oncogene cooperates with TGF-b1 to stimulate malignancy of carcinoma cells. Signaling events regulating migratory and invasive cell responses are less well characterized than those leading to uncontrolled cell proliferation. In this article, we discuss possible signaling pathways involved in malignant progression of mouse skin tumors.