Primary Response Genes Induced by Growth Factors and Tumor Promoters

Herschman, Harvey R.

doi:10.1146/annurev.bi.60.070191.001433

Cited by 1,028 publications

(428 citation statements)

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“…and is an important source of mitogens for cultured cells as well as for tissues during processes such as wound healing. The proliferative response to serum has been studied extensively and is characterized by the rapid activation of MAP kinase pathways and the induction of immediate early genes, many of which encode members of the AP-1 transcription factor family (c-fos and c-jun) (Herschman, 1991;Iyer et al, 1999). We found that serum stimulation of SCC cells causes a rapid increase in FGF-BP gene transcription and we have characterized this response with respect to the mechanisms of signal transduction.…”

Section: Introductionmentioning

confidence: 97%

Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is mediated through ERK and p38 MAP kinase activation and C/EBP-regulated transcription

et al. 2001

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The ®broblast growth factor-binding protein (FGF-BP) modulates FGF activity through binding and release from the extracellular matrix. Consequently, the expression of FGF-BP in certain tumor types is a rate-limiting regulator of FGF-mediated angiogenesis. FGF-BP is upregulated in squamous cell carcinoma by treatment with mitogens such as EGF or TPA. In this study, we investigated the regulation of FGF-BP gene expression by serum. Treatment of serum-starved ME-180 cells with fetal bovine serum (FBS) resulted in a rapid increase in steady-state levels of FGF-BP mRNA and in the rate of FGF-BP gene transcription. Serum induction of FGF-BP mRNA was not mediated through EGF receptor activation but was dependent on PKC, as well as ERK kinase (MEK) and p38 MAP kinase activation. Promoter analysis showed that C/EBP is the main promoter element required for the serum response. Unlike EGF-activation of FGF-BP, transcriptional induction by serum is not signi®cantly regulated through the AP-1 or E-box sites in the promoter. These results illustrate di erences between the mechanism of induction in response to serum and EGF. Oncogene (2001) 20, 1730 ± 1738.

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Section: Introductionmentioning

confidence: 97%

Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is mediated through ERK and p38 MAP kinase activation and C/EBP-regulated transcription

et al. 2001

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“…The induction of c-jun and c-fos transcription is one of the earliest nuclear responses to a wide variety of extracellular stimuli and is thought to be crucial in mediating cellular proliferating (Curran and Franza, 1988;Herschman, 1991). The mitogen stimulation of c-fos transcription is a paradigm for a gene regulated via the Ras pathway.…”

Section: Introductionmentioning

confidence: 99%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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“…Consequently, the transcriptional stimulation of immediate early genes is independent of protein synthesis. Several of these immediate early genes encode transcription factors which become engaged in the activation of delayed early genes (Herschman, 1991;Lau and Nathans, 1991). The proteins of the Fos and Jun families are among the best studied immediate early transcription factors and of relevance to this study.…”

Section: Introductionmentioning

confidence: 99%