title: Steering tumor progression through the transcriptional response to growth factors and stroma.
abstract: Tumor progression can be understood as a collaborative effort of mutations and growth factors, which propels cell proliferation and matrix invasion, and also enables evasion of drug-induced apoptosis. Concentrating on EGFR, we discuss downstream signaling and the initiation of transcriptional events in response to growth factors. Specifically, we portray a wave-like program, which initiates by rapid disappearance of two-dozen microRNAs, followed by an abrupt rise of immediate early genes (IEGs), relatively short transcripts encoding transcriptional regulators. Concurrent with the fall of IEGs, some 30-60 min after stimulation, a larger group, the delayed early genes, is up-regulated and its own fall overlaps the rise of the final wave of late response genes. This late wave persists and determines long-term phenotype acquisition, such as invasiveness. Key regulatory steps in the orderly response to growth factors provide a trove of potential oncogenes and tumor suppressors.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Morris E
authors.initials: ME
authors.lastname: Feldman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: yosef.yarden@weizmann.ac.il.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early; D018773:Genes, erbB-1; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D004815:Epidermal Growth Factor
keywords: Cancer immediate early genes; EGFR; Growth factors; Receptor tyrosine kinase; Transcription