Osteoblasts are target cells for transformation in c-fos transgenic mice

Grigoriadis, Agamemnon E.; Schellander, K.; Wang, Zhaoqi; Wagner, Erwin F.

doi:10.1083/jcb.122.3.685

Cited by 319 publications

(256 citation statements)

References 93 publications

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“…In contrast to these ®ndings, transgenic mice carrying either the H2-fosBLTR or the H2-cjunLTR construct did not develop any phenotypic abnormalities or tumours, despite high level expression of the transgene in a broad range of tissues (Grigoriadis et al, 1993). Given existing knowledge of these AP-1 family members, these results may have been unexpected.…”

Section: Discussioncontrasting

confidence: 63%

“…In the case of c-fos, over-expression of the gene under the control of either the metallothionein (MT) promoter (Ruther et al, 1987) or the H2-K b promoter (Grigoriadis et al, 1993), combined with replacement of 3' UTR mRNAdestabilising sequences with a viral long terminal repeat (LTR) sequence, resulted in development of lesions on the long bones of the legs. The further development of these lesions into osteosarcomas was variable and may have depended upon the level of expression of the transgene.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of fra-2 in transgenic mice perturbs normal eye development

et al. 1998

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Overexpression of fra-2 in transgenic mice perturbs normal eye development

et al. 1998

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“…The transcriptional regulation of fra-1 is unique among members of the fos gene family, since only fra-1 is subject to positive control by AP-1 activity (BruÈ sselbach et al, 1995;Bergers et al, 1995). The fra-1 gene is induced by ectopic expression of several members of the AP-1 family (c-Fos, v-Fos, FosB, Fra-1 and c-Jun) in several cell types (Bergers et al, 1995;Grigoriadis et al, 1993). Interestingly, the basal and AP-1 induced expression of fra-1 depends on regulatory sequences not only in the promoter region, but primarily in the ®rst intron which comprises a consensus AP-1 site and two TRE-like elements which di er by one nucleotide from the consensus AP-1 binding sequence (Bergers et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

et al. 1997

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We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to signi®cantly reduced serum stimulation of fra-1 expression in gene targeted mouse ®broblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA) n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two di erent crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.

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“…Since c-Fos is linked to osteosarcoma development from osteoblasts (Ruther et al, 1989;Grigoriadis et al, 1993), we first investigated if the tumor promoter sodium arsenite, hereafter referred to as As 3+ , activated c-fos expression in HOS cells. As 3+ treatment led to a robust induction of c-fos mRNA, albeit more slowly than epidermal growth factor (EGF) (Figure 1b).…”

Section: Arsenite Strongly Induces Ieg Transcription In Hos Cellsmentioning

confidence: 99%

Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF

et al. 2003

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Cellular stress activates multiple mitogen-activated protein kinase (MAPK) cascades and immediate-early gene (IEG) transcription. To address how these events are linked, we investigated the endogenous signaling/transcription factor network driving IEG activation by arsenite and anisomycin in the human osteosarcoma cell line HOS/TE-85. Induction of IEG transcription by both stresses corresponded temporally with the phosphorylation of the regulatory factors Elk-1 and cAMP response element-binding protein (CREB), along with activation of the extracellular signal-regulated kinase (ERK), stressactivated protein kinase (SAPK) and p38 MAPK cascades. To assess the role of the different cascades, they were selectively inhibited with PD98059, SP600125 and SB203580, respectively. This implicated all three cascades in Elk-1 phosphorylation after arsenite treatment, whereas ERK and SAPK inhibition diminished this, and IEG mRNA levels, downstream of anisomycin. SB blocked phosphorylation of both serum response factor (SRF) and CREB, and strongly reduced IEG activation by both stresses. Combining PD with SB further reduced arsenite induction of IEG transcription. Thus, all three MAPK cascades mediate anisomycin-and arseniteinduced signaling to IEG promoters in HOS cells through the differential targeting of Elk-1, SRF and CREB.

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Osteoblasts are target cells for transformation in c-fos transgenic mice

Abstract: Abstract. We have generated transgenic mice expressing the proto-oncogene c-fos from an H-2K b class I MHC promoter as a tool to identify and isolate cell populations which are sensitive to altered levels of Fos

Cited by 319 publications

References 93 publications

Overexpression of fra-2 in transgenic mice perturbs normal eye development

Overexpression of fra-2 in transgenic mice perturbs normal eye development

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF

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