GENE ACTIVATION IN MAMMARY CELLS

1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S346-S368 ◽  
Author(s):  
Roger W. Turkington ◽  
Nobuyuki Kadohama
Keyword(s):  
Cell Differentiation ◽  
Gene Transcription ◽  
Hormonal Regulation ◽  
Gene Activation ◽  
Milk Proteins ◽  
Mouse Mammary Gland ◽  
Nuclear Proteins ◽  
Mammary Cells ◽  
Alveolar Cells ◽  
Mammary Cell

ABSTRACT Hormonal activation of gene transcription has been studied in a model system, the mouse mammary gland in organ culture. Transcriptive activity is stimulated in mammary stem cells by insulin, and in mammary alveolar cells by prolactin and insulin. Studies on the template requirement for expression of the genes for milk proteins demonstrate that DNA methylation has an obligatory dependence upon DNA synthesis, but is otherwise independent from hormonal regulation of mammary cell differentiation. Incorporation of 5-bromo-2′deoxyuridine into DNA selectively inhibits expression of the genes for specific milk proteins. Undifferentiated mammary cells activate the synthesis of specific acidic nuclear proteins when stimulated by insulin. Several of these induced acidic nuclear proteins are undetectable in unstimulated undifferentiated cells, but appear to be characteristic components of the nuclei of differentiated cells. These results indicate that mammary cell differentiation is associated with a change in acidic nuclear proteins, and they provide evidence to support the concept that acidic nuclear proteins may be involved in the regulation of gene transcription and of mammary cell differentiation.

scholarly journals Regulation of mouse mammary cell differentiation by extracellular milk proteins

1991 ◽  
Vol 76 (3) ◽  
pp. 379-387 ◽  
Author(s):  
CJ Wilde ◽  
DR Blatchford ◽  
M Peaker
Keyword(s):  
Cell Differentiation ◽  
Milk Proteins ◽  
Mammary Cell

Differential effect of brefeldin A on phosphorylation of the caseins in lactating mouse mammary epithelial cells

1993 ◽  
Vol 106 (4) ◽  
pp. 1221-1226 ◽  
Author(s):  
M.D. Turner ◽  
S.E. Handel ◽  
C.J. Wilde ◽  
R.D. Burgoyne
Keyword(s):  
Differential Effect ◽  
Secretory Pathway ◽  
Mammary Epithelial Cells ◽  
Milk Proteins ◽  
Brefeldin A ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Secretory Proteins ◽  
Mammary Cells ◽  
Regulated Secretory Pathway

The major milk proteins, the caseins, contain multiple phosphorylation sites. Phosphorylation of the caseins is necessary to allow Ca2+ binding and aggregation of the caseins to form micelles. We have followed the phosphorylation of the caseins in isolated acini from lactating mouse mammary gland. Incubation of mammary cells with [32P]orthophosphate revealed that phosphorylation of newly synthesised caseins was complete within 20 minutes of synthesis. Extensive secretion of alpha-, beta- and gamma-caseins occurred over a 2 hour period. Activation of the regulated secretory pathway using ionomycin over the last hour resulted in a preferential increase in secretion of alpha- and gamma-caseins. Brefeldin A (BFA) inhibited protein secretion and synthesis in mammary cells in prolonged incubations. An examination of short-term treatments with BFA on 32P incorporation into the caseins revealed a differential effect of BFA in which the drug inhibited phosphorylation of beta- and gamma- but not alpha-caseins. These results suggest that phosphorylation of alpha-casein normally occurs in Golgi cisternae whereas that of beta- and gamma-caseins occurs in the trans-Golgi network. Phosphorylation of specific secretory proteins may, therefore, occur in different Golgi compartments.

scholarly journals Metabolism of the chemopreventive retinoid N-(4-hydroxyphenyl)retinamide by mammary gland in organ culture

1988 ◽  
Vol 256 (2) ◽  
pp. 579-584 ◽  
Author(s):  
R G Mehta ◽  
T A Hultin ◽  
R C Moon
Keyword(s):  
Mammary Gland ◽  
Organ Culture ◽  
Steroid Hormones ◽  
Hormonal Regulation ◽  
Mammary Carcinogenesis ◽  
Reversed Phase ◽  
Mouse Mammary Gland ◽  
Mammary Cells ◽  
Chemically Induced ◽  
Chloroform Methanol

N-(4-Hydroxyphenyl)retinamide (4-HPR) is considered to be the most effective chemopreventive retinoid for chemically induced mammary carcinogenesis in rats. However, the mechanism of 4-HPR action in mammary cells is poorly understood. In the present study we examined the metabolism of 4-HPR in the mouse mammary gland in organ culture. Mammary glands excised from BALB/c mice were incubated with 4-HPR in the presence of insulin, prolactin and steroid hormones for 6 days. The glands were extracted with chloroform/methanol (2:1, v/v), and the metabolites were separated on a reversed-phase h.p.l.c. column. Three metabolites were separated in addition to 4-HPR; one of the metabolites, M2, was co-eluted with 13-cis-4-HPR, M3 was co-eluted with N-(4-methoxyphenyl)retinamide (4-MPR) and M1 remains unidentified. There appeared to be some hormonal regulation in the distribution of metabolites in the glands. Increased levels of 4-MPR and M1 were observed in insulin-plus-prolactin-treated glands as compared with the glands incubated with steroid hormones. Furthermore, it was observed that M1 isolated from the livers of 4-HPR-treated rats competed for the cellular retinoic acid-binding protein (CRABP) sites; however, 4-HPR did not bind to CRABP. These results indicate that mouse mammary gland can metabolize 4-HPR and that the metabolites which compete for CRABP sites may have physiological significance in the retinoid inhibition of mammary carcinogenesis.

scholarly journals Respiratory Failure Due to Differentiation Arrest and Expansion of Alveolar Cells following Lung-Specific Loss of the Transcription Factor C/EBPα in Mice

2006 ◽  
Vol 26 (3) ◽  
pp. 1109-1123 ◽  
Author(s):  
Daniela S. Bassères ◽  
Elena Levantini ◽  
Hongbin Ji ◽  
Stefano Monti ◽  
Shannon Elf ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Respiratory Failure ◽  
Leucine Zipper ◽  
Type I ◽  
Type Ii ◽  
Alveolar Cells ◽  
Proliferating Cells ◽  
Therapeutic Benefits ◽  
Factor C

ABSTRACT The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBPα) inhibits proliferation and promotes differentiation in various cell types. In this study, we show, using a lung-specific conditional mouse model of C/EBPα deletion, that loss of C/EBPα in the respiratory epithelium leads to respiratory failure at birth due to an arrest in the type II alveolar cell differentiation program. This differentiation arrest results in the lack of type I alveolar cells and differentiated surfactant-secreting type II alveolar cells. In addition to showing a block in type II cell differentiation, the neonatal lungs display increased numbers of proliferating cells and decreased numbers of apoptotic cells, leading to epithelial expansion and loss of airspace. Consistent with the phenotype observed, genes associated with alveolar maturation, survival, and proliferation were differentially expressed. Taken together, these results identify C/EBPα as a master regulator of airway epithelial maturation and suggest that the loss of C/EBPα could also be an important event in the multistep process of lung tumorigenesis. Furthermore, this study indicates that exploring the C/EBPα pathway might have therapeutic benefits for patients with respiratory distress syndromes.

The pattern of cytokeratin synthesis is a marker of type 2 cell differentiation in adult and maturing fetal lung alveolar cells

1988 ◽  
Vol 129 (2) ◽  
pp. 505-515 ◽  
Author(s):  
Robert Paine ◽  
Avri Ben-Ze'ev ◽  
Stephen R. Farmer ◽  
Jerome S. Brody
Keyword(s):  
Cell Differentiation ◽  
Fetal Lung ◽  
Alveolar Cells

Regeneration of mammary glands in vivo from isolated mammary ducts

Development ◽  
1986 ◽  
Vol 96 (1) ◽  
pp. 229-243
Author(s):  
E. Jane Ormerod ◽  
Philip S. Rudland
Keyword(s):  
Epithelial Cells ◽  
Milk Fat ◽  
Cell Types ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Basal Cells ◽  
Alveolar Cells ◽  
Terminal End Buds ◽  
Mammary Cell

Rat mammary ducts, free of buds, can alone regenerate complete mammary trees when transplanted into the interscapular fat pads of syngeneic host rats. All the main mammary cell types are identified within such outgrowths. Epithelial cells, which show the presence of milk fat globule membrane antigens and microvilli on their luminal surfaces, line the ducts. Basal cells surrounding the ducts show characteristic features of myoepithelial cells: immunoreactive actin and keratin within the cytoplasm, myofilaments, pinocytotic vesicles and hemidesmosomal attachments to the basement membrane. Cells within the end buds and lateral buds, however, show few if any cytoplasmic myofilaments and are relatively undifferentiated in appearance. Intermediate morphologies between these cells and myoepithelial cells are seen nearer the ducts. In this respect they exactly resemble the cap cells found in terminal end buds (TEBs) of normal mammary glands. Occasional epithelial cells within alveolar buds show the presence of immunoreactive casein, which is a product of secretory alveolar cells in the normal rat mammary gland. Dissected terminal end buds can regenerate similar ductal outgrowths. Thus, ductal tissue alone can generate all the major mammary cell types seen in the normal gland, including the cap cells.

Sign in / Sign up

Export Citation Format

Share Document