Figure 8. Model for progression of nitrosamine-induced bladder carcinogenesis.
BBN-induced invasive carcinoma of the mouse bladder arises from basal stem cells that express Shh and CK5. Normal basal cells accumulate mutations at early stages of carcinogenesis and initiate clonal expansions to form intermediate CIS lesions, as indicated by green, yellow, and red colors. During this process, one or two clones become dominant and expand to repopulate the entire urothelium, generating mono/oligo clonal CIS lesions. CIS basal cells in one of these lesions then lose expression of Shh upon establishment of invasive carcinoma.