Impaired mammary gland development in Cyl-1(-/-) mice during pregnancy andlactation is epithelial cell autonomous

Citation
V. Fantl et al., Impaired mammary gland development in Cyl-1(-/-) mice during pregnancy andlactation is epithelial cell autonomous, DEVELOP BIO, 212(1), 1999, pp. 1-11
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENTAL BIOLOGY
ISSN journal
0012-1606 → ACNP
Volume
212
Issue
1
Year of publication
1999
Pages
1 - 11
Database
ISI
SICI code
0012-1606(19990801)212:1<1:IMGDIC>2.0.ZU;2-P
Abstract
A specific defect of mice lacking cyclin D1 (Cyl-1(-/-)) is impaired develo pment of the mammary gland during pregnancy. Here we show that when tissue from Cyl-1(-/-) mammary gland was transplanted into empty mammary fat pad o f wild-type mice, the abnormal phenotype was maintained, indicating that it is epithelial cell autonomous. Nevertheless, in pregnancy the early prolif erative response, which is characterized by extensive side branching, still occurs in the absence of cyclin D1. However, the response is atypical due to a marked reduction in the formation of accompanying alveoli. This reduct ion and delay in alveolar development persists throughout pregnancy. Moreov er, although prolactin synthesis and release appear to be normal, lactogene sis is severely compromised. Consistent with the appearance of numerous sid e branches, progesterone receptor expression was readily detected in the ma mmary tissue of pregnant Cyl-1(-/-) mice, although there was a significant change in the ratio of the two (A and B) receptor isoforms. In Cyl-1(-/-) m ammary glands during late pregnancy there was a decrease in the abundance o f total and phosphorylated Stat5a, as well as delayed onset and substantial diminution of milk protein expression. The biochemical analysis suggests t hat there is a cumulative delay in growth and differentiation of the mammar y gland during pregnancy that results in a severely compromised gland when, at parturition, further development is curtailed by the abrupt change in h ormonal milieu. (C) 1999 Academic Press.