MUC1 peptide inhibits tumor cell proliferation by binding small-MUC1 protein
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Abstract:
Objective:To investigate the inhibitory mechanism of mucin 1 tandem repeats peptide (MUC1 peptide) against the proliferation of tumor cells. Methods: Jurkat, Raji, U937, MCF7, SMMC7721, activated T and RAW264.7 cells were cocultured with MUC1 peptide; the inhibitory effects of MUC1 peptide on these cells were observed. Jurkat cellinoculated BABL/c mouse model was established by s.c. injection of Jurkat cells, and then the tumorbearing mice were treated with MUC1 peptide. The protein interacting with MUC1 peptide was identified by GST pulldown assay. Results: MUC1 peptide inhibited the proliferation of Jurkat, Raji, U937, MCF7 and SMMC7721 cells, but had no measurable inhibitory effect on activated T cells and RAW264.7 cells. MUC1 peptide significantly inhibited the growth of implanted Jurkat tumors in BABL/c mice (P<0.05). The protein interacting with MUC1 peptide in the lysates of Jurkat and MCF7 cells was confirmed by GST pulldown assay, with its molecular weight being approximately 115 000. The protein could bind specifically to antiMUC1 tandem repeat antibodies (GP1.4 and HMPV) and antiMUC1 cytoplasmic domain antibody (Ab5), indicating it might be a novel isotype of MUC1, and it was named small MUC1 (sMUC1). Conclusion: MUC1 peptide can transduce growth inhibitory signal by interacting with small MUC1 on the surface of tumor cells.
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Supported by the National Natural Science Foundation of China (No.30972782); the Science and Technology Development Program of Jilin Province (No. 20080931)