TY - JOUR
T1 - Muc4/sialomucin complex in the mammary gland and breast cancer
AU - Carraway, Kermit L.
AU - Price-Schiavi, Shari A.
AU - Komatsu, Masanobu
AU - Jepson, Scott
AU - Perez, Aymee
AU - Carothers Carraway, Coralie A.
N1 - Funding Information:
We thank Dr. Shari Price-Shiavi for assistance with the figures. Experimental studies cited were supported by Grants CA 52498 and Ca 74072 from the National Institutes of Health, Grant BE-71064 from the American Cancer Society and by the Sylvester Comprehensive Cancer Center of the University of Miami.
PY - 2001/7
Y1 - 2001/7
N2 - MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, characterized by mucin tandem repeat domains and a transmembrane domain which associates it with the cell plasma membrane. Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protective mechanism(s) may be highjacked by some carcinomas, such as those of the breast, to increase tumor progression. Two mechanisms are proposed to contribute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-recognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-β, which are relieved during pregnancy to permit secretion of MUC4 into milk. These mechanisms are also abrogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.
AB - MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, characterized by mucin tandem repeat domains and a transmembrane domain which associates it with the cell plasma membrane. Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protective mechanism(s) may be highjacked by some carcinomas, such as those of the breast, to increase tumor progression. Two mechanisms are proposed to contribute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-recognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-β, which are relieved during pregnancy to permit secretion of MUC4 into milk. These mechanisms are also abrogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.
KW - Antiadhesion
KW - Breast carcinoma
KW - Epithelia
KW - ErbB2
KW - Mucin
KW - Regulation
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U2 - 10.1023/A:1011327708973
DO - 10.1023/A:1011327708973
M3 - Review article
C2 - 11547901
AN - SCOPUS:0035405011
SN - 1083-3021
VL - 6
SP - 323
EP - 337
JO - Journal of Mammary Gland Biology and Neoplasia
JF - Journal of Mammary Gland Biology and Neoplasia
IS - 3
ER -