Structure and biology of a carcinoma-associated mucin, MUC1.
Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the name.
Gendler
S J
SJ
Imperial Cancer Research Fund, London, United Kingdom.
Spicer
A P
AP
Lalani
E N
EN
Duhig
T
T
Peat
N
N
Burchell
J
J
Pemberton
L
L
Boshell
M
M
Taylor-Papadimitriou
J
J
D000595:Amino Acid Sequence; D000818:Animals; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000032:analysis / Q000235:genetics*
D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins