Analysis of the Secreted Novel Breast-Cancer-Associated MUC1/Zs Cytokine

摘要

We report a novel small protein derived from the MUC1 gene by alternative splicing that does not contain the MUC1 tandem repeat array. This protein termed MUCl/Zs (=MUCl/ZD) retains the same N-terminal MUC1 sequences as all MUC1 protein isoforms, that comprises the signal peptide and a subsequent stretch of thirty amino acids. The MUCl/ZD C-terminal 43 amino acids are novel and result from a reading frameshift engendered by a splicing event. Expression of MUCl/ZD was demonstrated by immunohistochemistry, immunoblotting, immunoprecipitation and an ELISA assay, using MUCl/ZD specific polyclonal and monoclonal antibodies. MUC1/ZD protein was expressed in cancerous tissues and epithelial cells comprising skin tissue- its expression did not parallel the mucinous MUC1 protein. MUC1/ZD protein is expressed in tissues as an oligomeric complex composed of disulfide-linked MUC1 /ZD monomers. Limited homology between the novel MUC1/ZD C-terminal 43 amino acids and the N-terminal region of CD14, an innate immunity protein, prompted investigations as to whether MUCl/ZD binds to bacteria. Using transfectants expressing the MUC1/ZD protein we demonstrated that MUCl/ZD recognized and bound to bacterial cell surfaces. Results presented here demonstrate the existence of a novel MUC1 protein isoform. MUC1/ZD, expressed in breast cancer and skin epithelial cells that participates in bacterial recognition.