In contrast to CEACAM1-4L, CEACAM1-4S failed to generate a tumor suppressor phenotype when re-expressed in r-HCC or mouse colon carcinoma cell lines [13, 17, 18] . However when expressed in MCF7 mouse mammary carcinoma cells, CEA-CAM1-4S induced glandular morphogenesis, an activity requiring phosphorylation at one or more sites in the 4S cytoplasmic domain [19, 20, 21] . Site directed mutagenesis further showed that mutation of phenylalanine 445 at the C-terminus of the CEACAM1-4S cytoplasmic domain not only compromised interactions with the actin cytoskeleton but also inhibited lumen formation, suggesting interactions of CEACAM1-4S with the cytoskeleton were an important determinant of glandular morphogenesis. Interestingly, when mouse mammary carcinoma cells were grown in humanized NOD/SCID mouse mammary fat pads, only the 4L isoform initiated morphogenesis, the opposite of what was observed in vitro [21] , raising questions about the equivalence of in vitro and in vivo models of morphogenesis.