Characterization of the Mouse Epidermal Growth Factor Promoter and 5′-Flanking Region

Fenton, Suzanne E.; Groce, Natalie S.; Lee, Dong Hoon

doi:10.1074/jbc.271.48.30870

Cited by 22 publications

(19 citation statements)

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“…Based on our mA1ARp truncation, mutation, and gel-shift studies, we believe that the "A" motif is a Nkx2.5 binding site. The "B" motif appears to be an unconventional TATA box similar to that reported for other genes (29,30). Whereas there is evidence for two transcriptional start sites in the human A1ARp, we only observed one transcriptional start site for the murine A1AR promoter.…”

Section: Discussionsupporting

confidence: 84%

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Rivkees

Chen

Kulkarni

et al. 1999

Journal of Biological Chemistry

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Adenosine acts via A1 adenosine receptors (A1ARs) in the heart and brain to potently influence mammalian physiology. A1ARs are expressed very early in embryonic development, and A1ARs are among the earliest expressed G protein coupled receptors in the heart and brain. To understand the biologic basis of A1AR expression, a genomic fragment containing the murine A1AR promoter was cloned. Reporter assay studies using DDT1 MF2 cells that express A1ARs revealed that 500 base pairs of the proximal A1AR promoter contained essential elements for A1AR gene expression. Transgenic mice with A1AR proximal promoter coupled with the ␤-galactosidase reporter gene had heavy labeling of the brain and atria, consistent with normal patterns of A1AR expression. Within the proximal A1AR promoter, putative binding sites for cardiac transcription factors GATA and Nkx2.5 were identified. Co-expression studies revealed that GATA-4 and Nkx2.5 could individually drive A1AR promoter activity and act synergistically to activate A1AR expression. These observations suggest that embryonic A1AR expression involves activation of the A1AR promoter by GATA-4 and Nkx2.5.

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Section: Discussionsupporting

confidence: 84%

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Rivkees

Chen

Kulkarni

et al. 1999

Journal of Biological Chemistry

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“…In the present study, we found that the abundance of EGF mRNA is increased in H3122/TR cells. Given that the EGF gene contains consensus binding sequences for many transcription factors, including NF-kB, AP-1, AP-2, AP-3, and SP1 (16), such factors may play a role in the upregulation of EGF expression observed in our study.…”

Section: Discussionmentioning

confidence: 66%

Activation of HER Family Signaling as a Mechanism of Acquired Resistance to ALK Inhibitors in EML4-ALK–Positive Non–Small Cell Lung Cancer

Tanizaki

Okamoto

Okabe

et al. 2012

Clinical Cancer Research

147

101

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Purpose: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubuleassociated protein-like 4 (EML4)-ALK fusion protein. However, acquired resistance to these agents has already been described in treated patients, and the mechanisms of such resistance remain largely unknown.Experimental Design: We established lines of EML4-ALK-positive H3122 lung cancer cells that are resistant to the ALK inhibitor TAE684 (H3122/TR cells) and investigated their resistance mechanism with the use of immunoblot analysis, ELISA, reverse transcription and real-time PCR analysis, and an annexin V binding assay. We isolated EML4-ALK-positive lung cancer cells (K-3) from a patient who developed resistance to crizotinib and investigated their characteristics.Results: The expression of EML4-ALK was reduced at the transcriptional level, whereas phosphorylation of epidermal growth factor receptor (EGFR), HER2, and HER3 was upregulated, in H3122/TR cells compared with those in H3122 cells. This activation of HER family proteins was accompanied by increased secretion of EGF. Treatment with an EGFR-TKI induced apoptosis in H3122/TR cells, but not in H3122 cells. The TAE684-induced inhibition of extracellular signal-regulated kinase (ERK) and STAT3 phosphorylation observed in parental cells was prevented by exposure of these cells to exogenous EGF, resulting in a reduced sensitivity of cell growth to TAE684. K-3 cells also manifested HER family activation accompanied by increased EGF secretion.Conclusions: EGF-mediated activation of HER family signaling is associated with ALK-TKI resistance in lung cancer positive for EML4-ALK.

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“…The reduced expression of EGF may contribute to the decrease in EGFR signaling. Detailed analysis of the EGF promoter indicates the presence of multiple regulatory elements, including two AP-1 sites (20).…”

Section: Discussionmentioning

confidence: 99%

The c-Jun NH ₂ -terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis

Weston

Wong

Hall

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein kinases is activated in response to a wide array of cellular stresses and proinflammatory cytokines. Roles for JNK in the developing nervous system and T-cell-mediated immunity have been established by detailed studies of mice with compound mutations in the Jnk genes. However, little is known concerning the roles of JNK in other mammalian tissues. Mice lacking both of the ubiquitously expressed isoforms (JNK1 and -2) die during midgestation with neural tube closure defects and brain abnormalities. Here we show that JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, and lungs. In addition, JNK-deficient mice exhibit an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF. We further demonstrate that adult mice lacking either JNK1 or -2 display striking differences in epidermal proliferation and differentiation, indicative of distinct roles for these kinases in the skin. We conclude that JNK is necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis.

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Characterization of the Mouse Epidermal Growth Factor Promoter and 5′-Flanking Region

Cited by 22 publications

References 50 publications

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Activation of HER Family Signaling as a Mechanism of Acquired Resistance to ALK Inhibitors in EML4-ALK–Positive Non–Small Cell Lung Cancer

The c-Jun NH ₂ -terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis

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Characterization of the Mouse Epidermal Growth Factor Promoter and 5′-Flanking Region

Cited by 22 publications

References 50 publications

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Characterization of the Murine A1 Adenosine Receptor Promoter, Potent Regulation by GATA-4 and Nkx2.5

Activation of HER Family Signaling as a Mechanism of Acquired Resistance to ALK Inhibitors in EML4-ALK–Positive Non–Small Cell Lung Cancer

The c-Jun NH 2 -terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis

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The c-Jun NH ₂ -terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis