Both cell substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the posttranscriptional level.

Eisenstein, Richard S.; Rosen, Jeffrey M.

doi:10.1128/mcb.8.8.3183

Cited by 84 publications

(38 citation statements)

References 53 publications

(47 reference statements)

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“…Another tissue addressed by our studies is the mechanism by which Prl regulates gene expression in its target tissues. A handful of Prl-regulated, differentiationspecific marker genes from mammary gland tissue appear to be regulated by Prl primarily at the posttranscriptional level (11,36), although a specific effect of Prl on gene transcription has been observed (9; H. S. Goodman and J. M. Rosen, J. Cell Biol.…”

Section: ---------------------A-------g---c-t----g-------ac-ca -----mentioning

confidence: 99%

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Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells.

Yu-Lee¹,

Hrachovy²,

Stevens³

et al. 1990

Mol. Cell. Biol.

144

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The pituitary peptide hormone prolactin (Prl) is a potent inducer of Nb2 T lymphoma cell proliferation. To analyze the early genetic response to the mitogenic signals of Pri, a cDNA library was constructed from Nb2 T cells stimulated for 4 h with Prl and the protein synthesis inhibitor cycloheximide. Of 26 distinct clones isolated by differential screening, one clone, designated c25, exhibited extremely rapid but transient kinetics of induction by Prl and superinduction by Prl plus cycloheximide. Run-on transcription analysis indicated that c25 gene transcription was induced greater than 20-fold within 30 to 60 min of Prl stimulation. Surprisingly, DNA sequence analysis of c25 cDNA revealed that this Prl-inducible early-response gene is the rat homolog of the mouse transcription factor interferon-regulatory factor 1 (IRF-1), sharing 91% coding sequence similarity with mouse IRF-1. At the protein level, rat IRF-1 shares 97% and 92% homology with mouse IRF-1 and human IRF-1, respectively, suggesting that this molecule has been functionally conserved throughout evolution. Our studies show that the gene for IRF-1 is an immediate-early gene in Prl-stimulated T cells, which suggests that IRF-1 is a multifunctional molecule. In addition to its role in regulating growth-inhibitory interferon genes, IRF-1 may, therefore, also play a stimulatory role in cell proliferation. The gene for IRF-1 is one of the earliest genes known to be transcriptionally regulated by Prl.

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Section: ---------------------A-------g---c-t----g-------ac-ca -----mentioning

confidence: 99%

“…The pituitary hormone prolactin (Prl) has been shown to be a differentiation-specific and potent growth-promoting factor for a wide variety of tissues (11,14,20,31,38,41,45,46). Relatively little is known about the initial biochemical and genetic responses elicited by Prl binding to Prl receptors in these target tissues.…”

mentioning

confidence: 99%

Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells.

Yu-Lee¹,

Hrachovy²,

Stevens³

et al. 1990

Mol. Cell. Biol.

144

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“…Except for mouse line 5155, in which only a 3-fold increase was observed, the 19-to 70-fold increase in CAT activity in the mammary gland of mice 5087 and 2189 from virgin to lactation may reflect both the 10-to 20-fold increase in the percentage of epithelial cells in the mammary gland during this developmental period (22) and a 2-to 4.5-fold increase in the rate of transcription initiation induced by prolactin (7,10). The smaller induction in CAT activity observed in mouse line 5155 most likely reflects the site of integration of the transgene.…”

Section: Figmentioning

confidence: 99%

“…The ultimate function of the female mammary epithelium is to synthesize and secrete milk. Milk protein gene expression is regulated by a variety of factors, including peptide and steroid hormones and cell-cell and cell-substratum interactions (7,15,36). Caseins are the predominant milk proteins encoded by a small gene family, whose expression exhibits both tissue and stage specificity.…”

mentioning

confidence: 99%

Differential regulation of rat beta-casein-chloramphenicol acetyltransferase fusion gene expression in transgenic mice.

Lee¹,

Atiee²,

Rosen³

1989

Mol. Cell. Biol.

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Previous studies in our laboratory have demonstrated the mammary-specific expression of the entire rat j-casein gene with 3.5 kilobases (kb) of 5' and 3.0 kb of 3' DNA in transgenic mice (Lee et al., Nucleic Acids Res. 16:1027-1041. In an attempt to localize sequences that dictate this specificity, lines of transgenic mice carrying two different rat I8-casein promoter-bacterial chloramphenicol acetyltransferase (cat) fusion genes have been established. Twenty and eight lines of transgenic mice carrying two fusion genes containing either 2.3 or 0.5 kb, respectively, of 5'-flanking DNA of the rat 0-casein gene along with noncoding exon I and 0.5 kb of intron A were identified, most of which transmitted the transgenes to their offspring in a Mendelian pattern. CAT activity was detected predominantly in the lactating mammary gland of female transgenic mice but not in the male mammary fat pad. A several-hundred-fold variation in the level of cat expression was observed in the mammary gland of different lines of mice, presumably due to the site of integration of the transgenes. CAT activity was increased in the mammary gland during development from virgin to midpregnancy and lactation. Unexpectedly, the casein-cat transgenes were also expressed in the thymus of different lines of both male and female mice, in some cases at levels equivalent to those observed in the mammary gland, and in contrast to the mammary gland, CAT activity was decreased during pregnancy and lactation in the thymus. Thus, 0.5 kb of 5'-flanking DNA of the rat ,l-casein gene along with noncoding exon I and 0.5 kb of intron A are sufficient to target bacterial cat gene expression to the mammary gland of lactating mice.Development of the fetal mammary gland is characteristically sexually dimorphic (35). The ultimate function of the female mammary epithelium is to synthesize and secrete milk. Milk protein gene expression is regulated by a variety of factors, including peptide and steroid hormones and cell-cell and cell-substratum interactions (7,15,36). Caseins are the predominant milk proteins encoded by a small gene family, whose expression exhibits both tissue and stage specificity. The rat 1-casein gene encodes the principal murine casein and displays a several-hundred-fold increase in expression during adult mammary development from virgin to midlactation (12). Thus, it should provide an excellent model to elucidate the molecular mechanisms by which milk protein gene expression is regulated.The ability to introduce cloned or manipulated genes into mice via microinjection into fertilized eggs provides a novel approach to studying the regulation of gene expression (24), especially for those genes whose regulation requires cell-cell and cell-substratum interactions. An increasing number of cellular genes have been introduced into mice, and most of them resembling their mouse counterparts have been expressed and regulated correctly (25).We have previously generated several lines of transgenic mice, bearing the entire rat p-casein gene along with 3....

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“…Expression of milk protein genes in murine (Eisenstein and Rosen, 1988) and bovine (Huynh et al, 1991) cells, grown in culture, are affected by extracellu-lar matrix constituents and cell-cell interactions. The ability to develop and maintain polarity, where cells are allowed to orientate in an epithelial tissue layer, with opposite basal and luminal sides also seems necessary (Streuli et al, 1991).…”

Section: Intracellular Metabolismmentioning

confidence: 99%

Towards a mechanistic model of amino acid uptake and metabolism by the mammary gland of the lactating dairy cow: A literature review

Mass¹,

France²,

McBride³

1998

J. Anim. Feed Sci.

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A,review is given of information available to produce a dynamic mechanistic model of amino acid uptake and subsequent intracellular metabolism including milk and tissue protein synthesis within the lactating bovine mammary gland. To be a truly mechanistic representation of actual biology the model must address each AA individually, uptake via transporters must be described bidirectionally as has been observed in vitro and in vivo, and the requirements for all mammary origin milk proteins including oc-lactalbumin and B-lactoglobulin must be addressed. A conceptual framework for such a model is advanced.

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Both cell substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the posttranscriptional level.

Cited by 84 publications

References 53 publications

Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells.

Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells.

Differential regulation of rat beta-casein-chloramphenicol acetyltransferase fusion gene expression in transgenic mice.

Towards a mechanistic model of amino acid uptake and metabolism by the mammary gland of the lactating dairy cow: A literature review

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