Uteroglobin promoter-targeted c-MYC expression in transgenic mice cause hyperplasia of Clara cells and malignant transformation of T-lymphoblasts and tubular epithelial cells

• Published in: Transgenic research 2001-12, Vol.10 (6), p.501-511
• Main Authors: GEICK, Anke, REDECKER, Peter, EHRHARDT, Anja, KLOCKE, Rainer, PAUL, Dieter, HALTER, Roman
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Biological and medical sciences; Biotechnology; Blotting, Northern; Blotting, Southern; c-myc gene; Cell Transformation, Neoplastic; Cells; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; Epithelial Cells - pathology; Fundamental and applied biological sciences. Psychology; Genetic engineering; Genetic technics; Genetics of eukaryotes. Biological and molecular evolution; Green Fluorescent Proteins; Humans; Hyperplasia; Immunohistochemistry; In Situ Hybridization; Kidney - cytology; Luminescent Proteins - metabolism; Lung - cytology; Lung - pathology; Methods. Procedures. Technologies; Mice; Mice, Transgenic; Models, Genetic; Phenotype; Proto-Oncogene Proteins c-myc - biosynthesis; Proto-Oncogene Proteins c-myc - genetics; Rodents; Spleen - pathology; T-Lymphocytes - pathology; Transgenic animals; Transgenic animals and transgenic plants; Uteroglobin; Uteroglobin - genetics; Vertebrata
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1023/A:1013085228119

To investigate the influence of the proto-oncogene c-MYC on tumor development in different epithelial tissues which secrete Clara Cell Secretory Protein (uteroglobin, UG), transgenic mouse lines were established expressing the human c-MYC proto-oncogene under the control of the rabbit UG-promoter. These mice expressed the c-MYC transgene in Clara cells and other UG expressing tissues like uterus and prostate. In the bronchioalveolar epithelium of the lung hyperplasias developed originating from Clara cells. Surprisingly, transgenics most frequently developed T-lymphoblastic lymphomas, a polycystic kidney phenotype and renal cell carcinoma derived from tubular epithelial cells, which are both tissues that had so far not been known to express UG. Immunohistological studies in UG/MYC transgenics and in a transgenic line (UG/eGFP) expressing Green Fluorescent Protein confirmed that the uteroglobin promoter is not only active in Clara cells, but also in tubular epithelial cells of the kidney and in lymphatic tissue. The UG/MYC transgenics will be useful to investigate the biochemical mechanisms underlying the development of carcinomas and the oncogenic properties of c-MYC in epithelial cells of various tissues.