title: ETV1 positively regulates transcription of tumor suppressor ARF.
abstract: ETV1 (ETS variant 1) is a transcription factor from the ETS family and an oncogene in several types of human malignancies. Paradoxically, a predicted inactivating mutation in ETV1 was previously found in a clone of HT1080 cells with reduced activity of p53. We report that elevated expression of ETV1 makes p53-null tumor cells hypersensitive to restoration of said tumor suppressor. Furthermore, elevated levels of either wild-type ETV1 or its truncated derivative, dETV1, which mimics the product of an oncogenic rearrangement in certain tumors, results in increased expression of mRNA for p14ARF, a known activator of p53. Accordingly, expression of a luciferase reporter, which is driven by a putative ARF promoter, was elevated by concomitant expression of either ETV1 or dETV1. Our observations point to yet another example of a tumor suppressor gene being activated by a potentially oncogenic signal. A better understanding of the mechanisms that allow a cell to bypass such safeguards is needed in order to predict and prevent the development of an oncogene-tolerant state during cancer evolution.
authors.affiliation: Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Zynda
authors.affiliation: Department of Pathology; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Jackson
authors.affiliation: Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Partho
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Kandel
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D014157:Transcription Factors; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53
keywords: ETV1; oncogenic transformation; p14ARF; p53; tumor suppression