C/EBP beta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development

Citation
Tn. Seagroves et al., C/EBP beta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development, MOL ENDOCR, 14(3), 2000, pp. 359-368
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
MOLECULAR ENDOCRINOLOGY
ISSN journal
0888-8809 → ACNP
Volume
14
Issue
3
Year of publication
2000
Pages
359 - 368
Database
ISI
SICI code
0888-8809(200003)14:3<359:CB(BPC>2.0.ZU;2-4
Abstract
Deletion of the transcription factor CCAAT/enhancer binding protein (C/EBP) beta results in a severe inhibition of lobuloalveolar development in the mo use mammary gland. Because progesterone receptor (PR) is requisite for alve olar development, the expression of PR was investigated in C/EBP beta(-/-) mice. Unexpectedly, the number of PR-positive cells, as well as the levels of PR mRNA, were elevated 3-fold in the mammary glands of C/EBP beta(-/-) m ice. Furthermore, in contrast to wild-type nulliparous mice, in which PR di stribution shifted from a uniform to nonuniform pattern between 8-12 weeks of age, C/EBP beta(-/-) mice exhibited uniform PR distribution throughout a ll stages of mammary development analyzed. No change in C/EBP beta mRNA lev els was observed in the mammary glands of PR-/- mice, suggesting that PR ac ts in a pathway either in parallel to or downstream of C/EBP beta. The over expression and disrupted cellular distribution of PR in C/EBP beta(-/-) mic e were coincident with a striking 10-fold decrease in cell proliferation af ter acute steroid hormone treatment, assayed by incorporation of bromodeoxy uridine. In wild-type mice, PR and bromodeoxyuridine-positive cells were ad jacent to each other and rarely colocalized. No differences in the level or pattern of PR expression were observed in the uterus, suggesting that C/EB P beta influences PR in a mammary-specific fashion. Together, these data su ggest that C/EBP beta may control cell fate decisions in the mammary gland through the appropriate temporal and spatial expression of molecular marker s, such as PR, that induce the proliferation of alveolar progenitor cells v ia juxtacrine mechanisms.