Studies of Muc-1 mucin expression and polarity in the mouse mammary gland demonstrate developmental regulation of Muc-1 glycosylation and establish the hormonal basis for mRNA expression.
Muc-1 is a major mucin glycoprotein expressed on the surface of mammary epithelial cells. It has attracted considerable attention as it is expressed in an aberrant form on many breast tumor cells. Here we describe studies using a recently obtained cDNA probe of Muc-1 expression during lactogenic development in the mouse. Northern blot analysis demonstrated that Muc-1 is expressed at all stages of lactogenic development but its levels are increased very significantly during mid-pregnancy and into lactation. The basis of this was examined using CID-9 mammary epithelial cell cultures. It was found that in the presence of insulin Muc-1 mRNA levels were increased by both hydrocortisone and prolactin, with the combination of the three hormones supporting maximum expression. Muc-1 mRNA levels were also modulated by culturing cells on a basement-membrane-like extracellular matrix that promoted mRNA levels 5- to 10-fold above levels in cells cultured on plastic tissue culture dishes. Immunocytochemical studies using monoclonal antibodies to carbohydrate epitopes on Muc-1 demonstrated that while Muc-1 was found at all developmental stages, it became increasingly sialylated during the course of pregnancy and into lactation. Additionally, we found that while Muc-1 is tightly polarized to the apical surface of the epithelium of lactating and pregnant mice it exhibited a less-polarized distribution on a small proportion of ductal cells in virgin mice. We conclude that the expression of Muc-1 is regulated at several different levels and by a number of different factors. We speculate that this may reflect different functional roles for Muc-1 at different stages of mammary development.
Parry
G
G
Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Li
J
J
Stubbs
J
J
Bissell
M J
MJ
Schmidhauser
C
C
Spicer
A P
AP
Gendler
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal; D016764:Cell Polarity; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007774:Lactation; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry*; D051379:Mice; D009077:Mucins / Q000032:analysis / Q000235:genetics*; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D007328:Insulin; D009077:Mucins; D012333:RNA, Messenger; D011388:Prolactin; D006854:Hydrocortisone