Multihormonal Regulation of Milk Protein Gene Expression

Rosen, Jeffrey M.; Rodgers, John R.; Couch, C. H.; Bisbee, C. A.; David-Inouye, Yvonne; Campbell, Sheldon; Yu-Lee, Li-yuan

doi:10.1111/j.1749-6632.1986.tb15521.x

Cited by 46 publications

(11 citation statements)

References 38 publications

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“…Floating gel and a laminin substrata also allow high levels of a-lactalbumin expression in rat mammary cells (Wicha et a!., 1982). However, one of the major whey proteins in rodent milk, the whey acidic protein (WAP), is not expressed in cell culture, on floating gel, or on other culture conditions (Lee et a!., 1984Rosen et al, 1986). To our knowledge, none of the attempts to express high levels of WAP in cell culture has met with success.…”

Section: Introductionmentioning

confidence: 72%

A novel regulatory mechanism for whey acidic protein gene expression.

1989

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When primary mouse mammary epithelial cells (PMME) are cultured on a basement membrane type matrix, they undergo extensive morphogenesis leading to the formation of 3-dimensional alveoli-like spherical structures surrounding a closed lumen. We show for the first time that cells cultured on basement membrane-type matrix express high levels of whey acidic protein (WAP) mRNA and secrete the protein into the lumen. The expression of WAP appears to be dependent upon the formation of the alveoli-like spheres: prevention of sphere formation by fixation or drying of the matrix abolishes the expression of WAP. Co-culturing PMME on native and fixed basement membrane matrix indicates that the suppression of WAP expression is dominant, thereby revealing the existence of a diffusible inhibitor(s). The inhibitory activity is present in the conditioned medium of PMME cultured on plastic surface and floating collagen gels, substrata that do not form alveoli and do not allow WAP expression. These findings are consistent with the model that the synthesis, or the action, of the WAP inhibitory factor is regulated by the tissue-like multicellular organization of mammary cells. When PMME do not have correct 3-dimensional structures, one (or more) inhibitor is secreted into the medium which suppresses WAP expression by an autocrine or paracrine mechanism. Nuclear run-on experiments suggest that the suppression of WAP expression is posttranscriptional. These results have obvious bearings on the understanding of the mechanisms by which cell-cell and cell-extracellular matrix interaction regulate tissue specific gene expressions.

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Section: Introductionmentioning

confidence: 72%

A novel regulatory mechanism for whey acidic protein gene expression.

1989

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“…The mechanisms by which this hormone increases expression of these proteins are not yet understood, but it can be speculated that increased levels of prolactin may increase the transcription of h-casein and WAP as well as the half-life of these proteins [31]. Furthermore, the stability of h-casein mRNA may also be enhanced by high prolactin levels [32], which could possibly explain the increased concentration of this protein in the milk of the pair-fed group. Therefore, dietary insults (such as energy restriction) seem to affect h-casein expression in the rat mammary gland, which also results in increased concentrations of h-casein in milk.…”

Section: Discussionmentioning

confidence: 96%

Effect of suboptimal nutrition during lactation on milk protein gene expression in the rat

Zubieta

Lönnerdal

2006

The Journal of Nutritional Biochemistry

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“…To pinpoint the cell type responsible for the nursing defects of MRTF-A mutant mothers, we examined markers of the different mammary cell types using RT-PCR analysis with RNA samples from mammary tissues of 8-week-old virgins and females at 14 days of pregnancy, 4 days of lactation, 12 days of lactation, and 4 days of involution. Transcripts encoding milk proteins (␣-lactalbumin, ␤-casein, and whey acidic protein) (3,41) were expressed normally at all stages in MRTF-A mutant mammary glands (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

Requirement of a Myocardin-Related Transcription Factor for Development of Mammary Myoepithelial Cells

Li¹,

Chang²,

Qi³

et al. 2006

Molecular and Cellular Biology

164

165

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The mammary gland consists of a branched ductal system comprised of milk-producing epithelial cells that form ductile tubules surrounded by a myoepithelial cell layer that provides contractility required for milk ejection. Myoepithelial cells bear a striking resemblance to smooth muscle cells, but they are derived from a different embryonic cell lineage, and little is known of the mechanisms that control their differentiation. Members of the myocardin family of transcriptional coactivators cooperate with serum response factor to activate smooth muscle gene expression. We show that female mice homozygous for a loss-of-function mutation of the myocardin-related transcription factor A (MRTF-A) gene are unable to effectively nurse their offspring due to a failure in maintenance of the differentiated state of mammary myoepithelial cells during lactation, resulting in apoptosis of this cell population, a consequent inability to release milk, and premature involution. The phenotype of MRTF-A mutant mice reveals a specific and essential role for MRTF-A in mammary myoepithelial cell differentiation and points to commonalities in the transcriptional mechanisms that control differentiation of smooth muscle and myoepithelial cells.

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Multihormonal Regulation of Milk Protein Gene Expression

Cited by 46 publications

References 38 publications

A novel regulatory mechanism for whey acidic protein gene expression.

A novel regulatory mechanism for whey acidic protein gene expression.

Effect of suboptimal nutrition during lactation on milk protein gene expression in the rat

Requirement of a Myocardin-Related Transcription Factor for Development of Mammary Myoepithelial Cells

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