Journal article
Epidermal Growth Factor Up-regulates the Transcription of Mouse Lon Homology ATP-Dependent Protease Through Extracellular Signal-Regulated Protein Kinase- and Phosphatidylinositol-3-Kinase-dependent Pathways
Experimental cell research, Vol.280(1), pp.97-106
2002
DOI: 10.1006/excr.2002.5621
PMID: 12372343
Abstract
Epidermal growth factor (EGF) induces tumorigenic transformation of mouse epidermal cells (JB6 P
+). We cloned a full-length EGF-responsive cDNA in JB6P
+ cells; EGF up-regulated mRNA expression of this gene 5- to 6-fold. The deduced amino acid sequence of this cDNA exhibited 84 and 96% homology with human and rat Lon homology ATP-dependent protease, respectively, and all conserved domains of Lon, such as ATPase/protease domains, are present in the mouse gene, indicating that this gene is mouse Lon. EGF increased the transcriptional rate without affecting the mRNA stability of m-Lon. The level of m-Lon in irreversibly transformed mouse epidermal cells (JB7) was 3.4-fold higher than that in parental JB6 P
+ cells. Similarly, human mammary epithelial cells overexpressing the proto-oncogene ErbB2 expressed significantly higher levels of Lon than normal mammary epithelial cells. EGF failed to regulate Lon expression in ERK-deficient JB6 P
− cells or cells that expressed the dominant-negative p85 P13-K regulatory unit. Furthermore, selective chemical blockers for MEK1 and P13-K (PD98059 and LY294002) inhibited EGF-mediated induction. Mitochondria-localized Lon protease plays a critical role in the regulation of mitochondrial gene expression and genome integrity. Disruption of mitochondrial homeostasis is a general characteristic of tumorigenic transformation. Thus, the role of Lon in tumor promotion warrants further study.
Details
- Title: Subtitle
- Epidermal Growth Factor Up-regulates the Transcription of Mouse Lon Homology ATP-Dependent Protease Through Extracellular Signal-Regulated Protein Kinase- and Phosphatidylinositol-3-Kinase-dependent Pathways
- Creators
- Yunfeng Zhu - West Virginia UniversityMei Wang - West Virginia UniversityHong Lin - West Virginia UniversityChuanshu Huang - York UniversityXianglin Shi - National Institute for Occupational Safety and HealthJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Experimental cell research, Vol.280(1), pp.97-106
- Publisher
- Elsevier Inc
- DOI
- 10.1006/excr.2002.5621
- PMID
- 12372343
- ISSN
- 0014-4827
- eISSN
- 1090-2422
- Language
- English
- Date published
- 2002
- Academic Unit
- Pathology
- Record Identifier
- 9984186521702771
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