Grg1 acts as a lung-specific oncogene in a transgenic mouse model

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 3; pp. 1294 - 1301
• Main Authors: ALLEN, Thaddeus, VAN TUYL, Minke, IYENGAR, Pratibha, JOTHY, Serge, POST, Martin, TSAO, Ming-Sound, LOBE, Corrinne G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.2006
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Animals; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Co-Repressor Proteins; Drosophila; Fundamental and applied biological sciences. Psychology; Genetic Vectors - genetics; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medical sciences; Mice; Mice, Transgenic; Molecular and cellular biology; NIH 3T3 Cells; Oncogenes; Pneumology; ras Proteins - metabolism; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - genetics; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Signal Transduction; Tumor Suppressor Protein p53 - metabolism; Tumors of the respiratory system and mediastinum; Up-Regulation; Lung disease; Animal model; Respiratory disease; Lung cancer; Lung; Rodentia; Transgenic animal; Gene overexpression; Malignant tumor; Respiratory system; Carcinogenesis; Vertebrata; Specificity; Mammalia; Mouse; Bronchus disease; Onc gene
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-1634

Groucho proteins are transcriptional corepressors that are recruited to gene regulatory regions by numerous transcription factors. Long isoforms, such as Grg1, have all the domains of the prototype Drosophila Groucho. Short Groucho proteins, such as Grg5, have only the amino-terminal Q and G/P domains. We generated Grg1 and Grg5 transgenic mice and found that Grg1 overexpression induces lung adenocarcinoma, whereas Grg5 overexpression does not. Coexpression of Grg5 with Grg1 reduces tumor burden. Grg1 and Grg5 both diminish p53 protein levels; however, only Grg1 overexpression induces elevated levels of ErbB1 and ErbB2 receptor tyrosine kinases. The molecular and biological changes that accompany tumor progression in Grg1 transgenic mice closely reiterate events seen in human lung cancer. We also found that within a human lung tumor tissue array, a significant number of carcinomas overexpress Grg1/TLE1. Our data suggest that Grg1 overexpression contributes to malignancy in human lung cancers.