TY - JOUR A1 - Andreú, Thomas A1 - Beckers, Thomas A1 - Thoenes, Eric A1 - Hilgard, Peter A1 - Melchner, Harald von T1 - Gene trapping identifies inhibitors of oncogenic transformation : the tissue inhibitor of metalloproteinases-3 (TIMP3) and collagen type I alpha2 (COL1A2) are epidermal growth factor-regulated growth repressors T2 - Journal of biological chemistry N2 - A gene trap strategy has been used to identify genes that are repressed in cells transformed by an activated epidermal growth factor (EGF)/EGF receptor signal transduction pathway. EGF receptor-expressing NIH3T3 cells (HER1 cells) were infected with a retrovirus containing coding sequences for the human CD2 antigen and for secreted alkaline phosphatase in the U3 region. By selecting for and against CD2 expression, we obtained clones in which the gene trap had integrated into genes selectively repressed by EGF. Two of these clones encoded for the secreted extracellular matrix proteins TIMP3 and COL1A2. We show here that both genes are downstream targets of RAS and are specifically repressed by EGF-induced transformation. Moreover, this strategy tags tumor suppressor genes in their normal chromosomal location, thereby improving target-specific screens for antineoplastic drugs. Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75871 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-758715 SN - 0021-9258 VL - 273.1998 IS - 22 SP - 13848 EP - 13854 PB - American Society for Biochemistry and Molecular Biology Publications CY - Bethesda, Md ER -