Chapter 8 : Mammalian Development and Human Cancer: from the Phage Group to the Genetics of Intestinal Cancer

Abstract:

This chapter focuses on the abiding interest in the intersection of mammalian development and human cancer. In this essay, a mouse model for intestinal cancer is discussed. To answer the question of what are the molecular and biological intersections of mammalian development and human cancer, one determines what neoplastic processes occur spontaneously in a mutant that has lost the function of a single developmental gene. In human cancer genetics, this case is approximated by families in which a mutant allele inherited in heterozygous form predisposes the individual to a particular cancer syndrome. The tumor lineage has somatically lost the remaining normal allele by one of several possible mitotic mechanisms. A full exploration of the intersection with normal mammalian development of the loss-of-function neoplasms requires analysis of embryos homozygous for the mutant allele. The chapter focuses on two genes: Apc on chromosome 18, in which the Min nonsense allele has been induced by ethylnitrosourea, and the first modifier-of-Min locus, Mom-1, on chromosome. In sections of Min-induced tumors, the expression of cellular markers for three differentiated cell types of the intestinal epithelium is detected by immunohistochemistry: the Paneth cell (lysozyme), the enteroendocrine cell (serotonin), and the enterocyte (fatty acid-binding protein). The properties of the tumor can in principle be altered by changes either in the provirus or in the source of any differential growth factors.