V-<i>Myc</i>Alters the Response of a Cloned Mouse Mammary Epithelial Cell Line to Lactogenic Hormones

Ball, Roland K.; Ziemiecki, Andrew; Schonenberger, Cora A.; Ernst, Rolf; Redmond, Shelagh; Groner, Bernd

doi:10.1210/mend-2-2-133

Cited by 29 publications

(7 citation statements)

References 63 publications

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“…To test whether the altered milk protein expression can also be observed on a cellular basis, we again used the mouse mammary gland derived cell line HC11, which can undergo a limited functional differentiation under appropriate hormonal stimulation [35] (Fig. 4E).…”

Section: Resultsmentioning

confidence: 99%

“…HC11 mammary epithelial cells [35] were routinely cultured in complete growth medium: RPMI 1640, 10% FBS, 60 µg/ml gentamicin, 2 mM glutamine (all from PAA), 20 µg/ml insulin from bovine pancreas (I6634; Sigma) and 10 ng/ml of EGF (E4127; Sigma). To induce competence to differentiate, 2-day confluent HC11 cells were incubated for 48 hours in medium without EGF and with low serum (2%).…”

Section: Methodsmentioning

confidence: 99%

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Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

et al. 2014

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Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15Ink4) or Cdkn1a (p21Cip1). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1ΔPOZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5 phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in Miz1ΔPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

et al. 2014

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“…A crucial difference in the consequences of H-ras and c-myc expression was also confirmed in cell culture. Whereas H-ras expression suppressed the lactogenic hormone response of mammary epithelial cells, c-myc expression did not inhibit the production of milk proteins upon hormonal stimulation (Ball et al, 1988).…”

Section: Experiments With the C-myc Oncogenementioning

confidence: 85%

Oncogene expression in mammary epithelial cells

Groner

1992

J of Cellular Biochemistry

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Mouse strains which develop tumors at a high incidence with characteristics very similar to human cancers have been derived over the last 8 years. The tumors are caused by defined genetic alterations in the mouse genome. Three areas of research have contributed to the derivation of these mouse strains: (1) Molecular analysis of human tumors has shown that distinct oncogenes and tumor suppressor genes are consistently involved in a high percentage of primary tumors. (2) Regulatory enhancer-promoter sequences have been identified which direct gene expression to specific target cells, preferentially mammary epithelial cells. (3) The introduction of recombinant DNA molecules into fertilized mouse eggs by microinjection and integration of the injected DNA into the genome of injected cells has given rise to mutant mouse strains with unique and defined genetic alterations. Studies with different promoter-oncogene combinations introduced into transgenic mouse strains have led to the following general conclusions: (1) Oncogenes expressed in mammary gland cells predispose transgenic mice to mammary tumors. (2) The oncogenic potential of individual oncogenes in mammary epithelial cells differs. (3) Oncogene expression initially often causes a preneoplastic state affecting growth and differentiation parameters of cells. (4) The expression of different oncogenes synergizes to reduce tumor latency. Synergism can also be observed with physiological growth signals like estrogen or growth hormone. The oncogenes with a role in mammary carcinomas which have been investigated in transgenic mice will be described here. The phenotypic consequences of oncogene expression and the implications for the multistep carcinogenesis model will be discussed.

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“…Introduction of oncogenes into a variety of epithelial cell lines repeatedly changes their phenotype and growth properties, and renders them tumorigenic in nude mice (Darter et al, 1986;Rijsewijk et al, 1987;Warren and Nelson, 1987;Ball et al, 1988;Redmond et al, 1988). However, the effects on apical-basolateral organization are not considered.…”

Section: Abbreviation Used In This Papermentioning

confidence: 99%

Multilayering and loss of apical polarity in MDCK cells transformed with viral K-ras.

Schoenenberger

Żuk

Kendall

et al. 1991

The Journal of Cell Biology

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Abstract. The effects of viral Kirsten ras oncogene expression on the polarized phenotype of MDCK cells were investigated. Stable transformed MDCK cell lines expressing the v-K-ras oncogene were generated via infection with a helper-independent retroviral vector construct. When grown on plastic substrata, transformed cells formed continuous monolayers with epithelial-like morphology. However, on permeable filter supports where normal cells form highly polarized monolayers, transformed MDCK cells detached from the substratum and developed multilayers. Morphological analysis of the multilayers revealed that oncogene expression perturbed the polarized organization of MDCK cells such that the transformed cells lacked an apical-basal axis around which the cytoplasm is normally organized. Evidence for selective disruption of apical membrane polarity was provided by immunolocalization of membrane proteins; a normally apical l l4-kD protein was randomly distributed on the cell surface in the transformed cell line, whereas normally basolateral proteins remained exclusively localized to areas of cell contact and did not appear on the free cell surface. The discrete distribution of the tight junction-associated ZO-1 protein as well as transepithelial resistance and flux measurements suggested that tight junctions were also assembled.These findings indicate that v-K-ras transformation alters cell-substratum and cell-cell interactions in MDCK cells. Furthermore, v-K-ras expression perturbs apical polarization but does not interfere with the development of a basolateral domain, suggesting that apical and basolateral polarity in epithelial ceils may be regulated independently.

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V-MycAlters the Response of a Cloned Mouse Mammary Epithelial Cell Line to Lactogenic Hormones

Cited by 29 publications

References 63 publications

Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

Oncogene expression in mammary epithelial cells

Multilayering and loss of apical polarity in MDCK cells transformed with viral K-ras.

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