Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells.
The response of mammary epithelial cells to basement membrane and stroma induced signals contributes to the degree of differentiation in this tissue. The studies reported here indicate that connective tissue growth factor (CTGF) is highly elevated during lactogenic differentiation of the HC11 mouse mammary epithelial cell line. In addition, CTGF is expressed in the mouse mammary gland during pregnancy and lactation and it is expressed in primary mammary epithelial cell cultures established from pregnant mice. In HC11 cells CTGF is transcriptionally regulated by dexamethasone, but not by estrogen or progesterone, and CTGF expression is not dependent on TGFbeta. CTGF contributes to and is required for lactogenic differentiation of HC11 cells, as demonstrated by increased differentiation following expression of plasmid-encoded CTGF and decreased differentiation following depletion of endogenous CTGF with siRNA. Moreover, HC11 mouse mammary epithelial cells infected with an adenoviral vector encoding CTGF exhibit increased lactogenic differentiation. Plasmid vector-induced elevation of CTGF levels also increased the level of beta1 integrin in HC11 cells. Because the production of stromal factors is an important component of differentiation in mammary epithelial cells, the regulation of CTGF by glucocorticoids may play a critical role in this aspect of the control of differentiation. The studies reported here provide important information on the role of CTGF in mammary epithelial cell differentiation.
Wang
Weihan
W
Department of Pathology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Morrison
Bethanie
B
Galbaugh
Traci
T
Jose
Cynthia C
CC
Kenney
Nicholas
N
Cutler
Mary Lou
ML
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology
C526318:CCN2 protein, mouse; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins; D003907:Dexamethasone; D011388:Prolactin; D008156:Luciferases