Neuregulin-regulated gene expression in mammary carcinoma cells.
Recent studies have suggested that autocrine production of Neuregulin (NRG), a growth factor that activates members of the Epidermal Growth Factor Receptor/ErbB family of proto-oncogenes, is sufficient for breast tumor initiation and progression. To elucidate the molecular mechanisms regulating these events, we undertook a global analysis of genes regulated by NRG in luminal mammary epithelial cell lines. Gene expression profiling of estrogen receptor-positive T47D cells exposed to NRG-1 revealed both previously identified and novel targets of NRG activation. Profiling of other estrogen receptor-positive breast cancer cell lines, MCF7 and SUM44, yielded a group of twenty-one genes whose transcripts are upregulated by NRG in all three lines tested. The NRG targets are FBJ murine osteosarcoma viral oncogene homolog B, Early growth response 1, v-jun avian sarcoma virus 17 oncogene homolog, Activating transcription factor 3, Homo sapiens cDNA FLJ31636 fis, Jun B proto-oncogene, Forkhead box C1, Platelet/endothelial cell adhesion molecule 1, NADPH-dependent retinol dehydrogenase/reductase, Dual specificity phosphatase 5, NGF inducible protein TIS21, Connective tissue growth factor, Jun D proto-oncogene, Serum response factor, Cullin 1, v-myc avian myelocytomatosis viral oncogene, Transient receptor potential channel 1, Low density lipoprotein receptor, Transforming growth factor beta 1, Nucleoporin 88 kDa, and Pleckstrin homology-like domain A1. Since NRG activation of these cells induces resistance to anti-hormonal therapy, the identified genes may provide clues to molecular events regulating mammary tumor progression and hormone independence.
Amin
Dhara N
DN
Department of Pathology, Yale University School of Medicine, BML-342, 310 Cedar Street, P.O. Box 208023, New Haven, CT 06520-8023, USA.
Tuck
David
D
Stern
David F
DF
D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas
D018076:DNA, Complementary; C000715470:MAS1 protein, human; C094131:NRG1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D000090063:Proto-Oncogene Mas