Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with changes in cell-cell adhesion.
The MUC1 epithelial mucin is expressed by glandular epithelial cells and is often highly expressed and associated with poor prognosis in adenocarcinomas. Tyrosine phosphorylation of the highly conserved cytoplasmic tail of MUC1 (MUC1-CT) has been demonstrated in MUC1 transfected cells and in one breast cancer cell line. In addition, associations between MUC1 and secondary signalling molecules have been demonstrated in breast cancer cell lines. MUC1 clearly plays a role in intracellular signalling, since we were able to demonstrate tyrosine phosphorylation of the MUC1-CT in breast and ovarian cancer cell lines and in primary cultures of serous ovarian cancers. We were unable to modulate MUC1-CT phosphorylation using conditioned media from cell lines showing the highest levels of signalling. However, in several breast and ovarian cancer cell lines, we clearly showed the highest levels of MUC1-CT tyrosine phosphorylation occurred during recolonisation of culture dishes or in low-density adherent cultures. We now hypothesise that phosphorylation changes may reflect either involvement of MUC1 in cell motility or a redistribution of MUC1 in the membrane during the course of cell-cell adhesion.
Mater Medical Research Institute, South Brisbane, Australia.
R J
RJ
Quin
M A
MA
McGuckin
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002021:Buffers; D002448:Cell Adhesion / Q000502:physiology; D017077:Culture Media, Conditioned; D003593:Cytoplasm / Q000378:metabolism; D003902:Detergents; D005260:Female; D006801:Humans; D018396:Mucin-1 / Q000378:metabolism* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011233:Precipitin Tests; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D002021:Buffers; D017077:Culture Media, Conditioned; D003902:Detergents; D018396:Mucin-1; D020033:Protein Isoforms; D014443:Tyrosine