title: The type 1 insulin-like growth factor receptor and resistance to DACH1.
abstract: The mammalian homolog of the Drosophila dachshund gene (DACH1) has been reported as a tumor suppressor in human breast and prostate cancers. It downregulates the epidermal growth factor receptor (EGFR) and cyclin D1. The signaling pathway of the type 1 insulin-like growth factor receptor (IGF-IR) is known to be responsible for the development of resistance to treatment of human cancer with antibodies to the EGFR. We have asked whether DACH1 still exerts its tumor suppressor activity in cells dependent on the IGF-IR for growth. We find that in cells growing in IGF-1 (and unresponsive to EGF), DACH1 is devoid of tumor suppressor activity.
authors.affiliation: Department of Cancer Biology, Jefferson Medical Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Tiziana
authors.initials: T
authors.lastname: DeAngelis
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
authors.forename: Richard
authors.initials: R
authors.lastname: Pestell
authors.forename: Renato
authors.initials: R
authors.lastname: Baserga
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005136:Eye Proteins / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C486747:DACH1 protein, human; C456264:Dach1 protein, mouse; D005136:Eye Proteins; D014157:Transcription Factors; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1