Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor

Oncogene
M KomatsuK L Carraway

Abstract

Overexpression of the membrane mucin MUC4/Sialomucin complex (SMC) has been observed during malignant progression of mammary tumors in both humans and rats, suggesting that deregulation of MUC4/SMC expression might facilitate development of these malignancies. As previously reported, overexpression of SMC results in suppression of both cell adhesion and immune killing of tumor cells. SMC also acts as a ligand for ErbB2/Neu, modulating phosphorylation of the receptor tyrosine kinase in the presence and absence of heregulin. The present studies investigated the effect of Muc4/SMC up-regulation on primary tumor growth using a tetracycline-inducible SMC expression system in a xenotransplanted tumor model. SMC up-regulation provoked rapid growth of transfected A375 melanoma in nude mice. Up-regulation of SMC, however, did not significantly increase proliferation of A375 cells in vitro. Instead, a strong suppression of apoptosis was observed in situ in SMC-overexpressing tumors. These data suggest that Muc4/SMC expression promotes tumor growth in vivo at least in part via suppression of tumor cell apoptosis. Importantly, reduction of apoptosis was also observed in vitro, indicating that anti-apoptotic effect of SMC is independent of ...Continue Reading

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