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Growth Factors Regulate Heterogeneous Nuclear Ribonucleoprotein K Expression and Function
- Source :
- Journal of Biological Chemistry. 276:9699-9704
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Epidermal growth factor (EGF) family of growth factors and their receptors regulate normal and cancerous epithelial cell proliferation, a process that can be suppressed by antireceptor blocking antibodies. To identify genes whose expression may be modulated by antireceptor blocking antibodies, we performed a differential display screen with cells grown in the presence or absence of antireceptor blocking antibodies; isolates from one cDNA clone were 100% identical to human heterogeneous nuclear ribonucleoprotein K (hnRNP K), a protein with a conserved KH motif and RGG boxes, has been implicated in such functions as sequence-specific DNA binding, transcription, RNA binding, and nucleocytoplasmic shuttling. Both EGF and heregulin-beta1 induced expression of hnRNP K mRNA and protein in human breast cancer cells. This growth factor-mediated hnRNP K expression was effectively blocked by pretreatment of cultures with humanized anti-EGF receptor (EGFR) antibody C225, or anti-human epidermal growth factor receptor-2 (HER2) antibody. Anti-EGFR monoclonal antibody also caused regression of human tumor xenografts and reduction in hnRNP K levels in athymic mice. Samples from grade III human breast cancer contained more hnRNP K protein than samples from grade II cancer. Finally, overexpression of hnRNP K in breast cancer cells significantly increased target c-myc promoter activity and c-Myc protein, hnRNP K protein levels, and enhanced breast cancer cell proliferation and growth in an anchorage-independent manner. These results suggested that the activity of human EGF receptor family members regulates hnRNP K expression by extracellular growth promoting signals and that therapeutic humanized antibodies against EGFR and HER2 can effectively block this function.
- Subjects :
- DNA, Complementary
Time Factors
Transcription, Genetic
Receptor, ErbB-2
medicine.drug_class
Neuregulin-1
Immunoblotting
Genes, myc
Mice, Nude
Breast Neoplasms
Biology
Ligands
Monoclonal antibody
Heterogeneous ribonucleoprotein particle
Biochemistry
Heterogeneous-Nuclear Ribonucleoproteins
Heterogeneous-Nuclear Ribonucleoprotein K
Proto-Oncogene Proteins c-myc
Mice
Epidermal growth factor
Blocking antibody
Tumor Cells, Cultured
medicine
Animals
Humans
Tissue Distribution
RNA, Messenger
Growth Substances
Promoter Regions, Genetic
Molecular Biology
Messenger RNA
Differential display
Epidermal Growth Factor
Gene Expression Profiling
Antibodies, Monoclonal
DNA
Cell Biology
Blotting, Northern
Precipitin Tests
Molecular biology
ErbB Receptors
Ribonucleoproteins
Cancer cell
Cell Division
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 276
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....2d09eec6a1ec351d29e78c7aaf02e9c9