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

Masanobu Komatsu, Scott Jepson, Maria E. Arango, Coralie A. Carothers Carraway, Kermit L. Carraway

Research output: Contribution to journalArticlepeer-review

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, over-expression 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 tumor-host interactions. These findings strongly suggest that SMC up-regulation alters intracellular signaling to favor cell survival, providing for the first time evidence for the regulation of programmed cell death by a gene of the MUC family.

Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalOncogene
Volume20
Issue number4
DOIs
StatePublished - Jan 25 2001
Externally publishedYes

Keywords

  • Apoptosis
  • ErbB2
  • Muc4
  • Sialomucin complex
  • Tumor growth
  • Xenotransplanted tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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