Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus

Huang, A L; Ostrowski, Michael C.; Berard, D S; Hager, Gordon L.

doi:10.1016/0092-8674(81)90408-6

Cited by 302 publications

(136 citation statements)

References 35 publications

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“…The p21 transformation (ras) gene from Harvey murine sarcoma virus, another glucocorticoid-unresponsive gene, was removed from its normal promoter, linked downstream of the MTV LTR, and introduced into NIH-3T3 cells which became transformed. The levels of p21 RNA and protein were increased in the presence of glucocorticoids (Huang et al, 1981). It should be noted that retroviral LTRs may behave as strong 'promoters' (in the broad sense) which exhibit the general property of activating, irrespective of glucocorticoid stimulation, the expression of heterologous gene coding sequences from which the natural promoter has been deleted (Joyner et al, 1982).…”

Section: Glucocorticoids Modulate Mrna Concentrationmentioning

confidence: 99%

Control of gene expression by glucocorticoid hormones

Rousseau¹

1984

Biochemical Journal

142

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Glucocorticoids control the expression of a small number of transcriptionally active genes by increasing or decreasing mRNA concentration. Either effect can result from a transcriptional or a post-transcriptional mechanism. Induction of mouse mammary tumour virus RNA results from a stimulation of transcription initiation and depends on the presence of defined regions in proviral DNA. These regions bind the glucocorticoid receptor and behave functionally as proto-enhancers. Glucocorticoid-inducible genes can retain their sensitivity to the hormone after transfer to a heterologous cell by transfection techniques. Non-inducible genes can become inducible when linked to the promoter region of an inducible gene. The mechanisms by which the receptor-steroid complex stimulates or inhibits transcription or influences mRNA stability are unknown. Receptor binding to nucleic acids appears to be a necessary but not sufficient condition. It is likely that the receptor also interacts with chromatin proteins. This might lead to a catalytic modification of these proteins, resulting in a modulation of gene expression. Development of glucocorticoid-sensitive, biochemically defined, cell-free transcription systems should provide a tool to delineate the molecular determinants of this essential regulatory mechanism.

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Section: Glucocorticoids Modulate Mrna Concentrationmentioning

confidence: 99%

Control of gene expression by glucocorticoid hormones

Rousseau¹

1984

Biochemical Journal

142

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“…The cDNA of mouse cyclin D3 was cloned into the EcoR1 site of an expression plasmid containing the mouse mammary tumor virus long terminal repeat (MMTV-LTR) plus SV40 intron and polyadenylation signals (Huang et al, 1981). The linearized MMTV-cyclin D3 plasmid containing plasmid sequences in addition to the MMTV-LTR cyclin D3 fragment was microinjected into FVB/n fertilized mouse oocytes and two transgenic founder mice were identified by Southern analysis of EcoR1 digest of tail genomic DNA.…”

Section: Generation Of Mmtv-cyclin D3 Transgenic Micementioning

confidence: 99%

Alternative mammary oncogenic pathways are induced by D-type cyclins; MMTV-cyclin D3 transgenic mice develop squamous cell carcinoma

et al. 2003

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The three human D-type cyclins, cyclin D1, D2 and D3 share the ability to bind to and activate cdk4 and 6. MMTV-cyclin D1 transgenic mice develop mainly adenocarcinoma, while MMTV-cyclin D2 mice show a lack of alveologenesis during pregnancy and only develop carcinoma at low frequency. The effect of cyclin D3 overexpression in mammary glands remains hitherto unknown. We generated MMTV-cyclin D3 transgenic mice and report here that they develop exclusively squamous cell carcinoma. We show that although cyclin D3 transgene expression was detected early in puberty, postnatal development and mammary gland proliferation were normal in virgin animals. In contrast, multiparous mice develop multiple foci of abnormal growth that correspond to various stages of squamous metaplasia. Therefore, our results support a role for cyclin D3 in squamous differentiation. In addition, we found that p16 expression during involution is abolished, while p27 expression increased in MMTV-cyclin D3 mice, two modifications that have been reported in the other MMTV-D-type cyclin transgenic models. Our observations indicate that despite biochemical redundancy in vitro and in vivo, D-type cyclins promote distinct oncogenic pathways.

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“…Age refers to 50% tumor free survival, T (days) MMTV promoter) (Huang et al, 1981) or vehicle alone (DMSO diluted 1 : 5000 in growth medium). In MMTV-Wnt-10b bearing WC3F cells (Figure 6e and f), colony number was stimulated 79% in dishes treated with 1610…”

Section: Mmtv-wnt-10b Mice Develop Stochastic Adenocarcinomas Of the mentioning

confidence: 99%

Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice

1997

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Wnt-10b is expressed during the formation of the mammary rudiment in mouse embryos and its expression continues through puberty when the mammary ductal pattern is established under control of ovarian steroids. Recently, viral activation of the Wnt-10b locus has linked its overexpression to mammary tumor formation, suggesting a role for Wnt-10b in patterning and growth-regulation of the mammary gland. To test this notion, we created lines of transgenic mice that express elevated levels of Wnt-10b under the control of the MMTV promoter/enhancer. Overexpression of this gene resulted in profound developmental alterations in the mammary gland, including expanded glandular development and the precocious appearance of alveoli in virgin females. Moreover, transgenic male mice also exhibited dramatic mammary development involving highly branched mammary ducts and gynecomastia. Aberrant expression of Wnt-10b in the mammary rudiments of males evidently bypasses the normal requirement for ovarian hormonal control in stimulating mammary ductal growth and the repressive eects of androgens. In addition to these developmental eects, transgenic mice of both sexes were highly susceptible to the development of mammary adenocarcinomas. Such tumors arose in a solitary manner indicating that Wnt10b is a proto-oncogene which provides a necessary, but insucient signal for oncogenesis. Relevant to this, there was no evidence of ampli®ed expression of FGF mRNAs in these tumors though the Fgf's are a class of genes often implicated as collaborators in Wnt-mediated tumor formation. Indeed, co-expression of MMTV-Wnt10b and MMTV-FGF-3/int-2 resulted in sterile ospring with highly disorganized mammary epithelium, demonstrating a potent interaction between their respective developmental pathways. These results suggest that Wnt-10b, or other Wnt genes expressed early in mammary development, play a role in regulating sexual dimorphism and show potent transforming activity when overexpressed.

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Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus

Cited by 302 publications

References 35 publications

Control of gene expression by glucocorticoid hormones

Control of gene expression by glucocorticoid hormones

Alternative mammary oncogenic pathways are induced by D-type cyclins; MMTV-cyclin D3 transgenic mice develop squamous cell carcinoma

Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice

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