Role of human CEACAM5 and CEACAM6 in murine lung tumorigenesis

C9 Human carcinoembryonic antigen (CEA or CEACAM5) and its close relative, CEACAM6, are often over-expressed in many cancers. While CEACAM5 and CEACAM6 have been shown to play a role in colon and pancreatic cancers, their relevance to lung cancer is presently unknown, although CEA is commonly used for diagnosis and prognostic evaluation of patients with cancers at this site. Transgenic mice expressing both human CEACAM5 and CEACAM6 in lung tissue (CEABAC mice) have been generated in FVB/N mice, which are prone to develop spontaneous lung tumors. Here we show that, although spontaneous lung tumors are far more prevalent in male than in female WT mice, in CEABAC mice the females selectively show a 5 to 7 fold higher lung tumor incidence than their WT counterparts, bringing the incidence above that of male mice. Mutations in K-ras, but not p53, can be detected in these lung tumors. The mechanism of this increase specifically in the female FVB/N mice is presently unknown. These results suggest a possible role of CEACAM5/CEACAM6 in human lung tumorigenesis which is female specific.