Uteroglobin promoter-targeted c-MYC expression in transgenic mice cause hyperplasia of Clara cells and malignant transformation of T-lymphoblasts and tubular epithelial cells |
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Authors: | Geick Anke Redecker Peter Ehrhardt Anja Klocke Rainer Paul Dieter Halter Roman |
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Affiliation: | (1) The Center for Medical Biotechnology, Fraunhofer Institute for Toxicology and Aerosol Research, Nikolai-Fuchs-Str. 1, D-30625 Hannover, Germany;(2) Present address: Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Auerbachstr. 112, D-70376 Stuttgart, Germany;(3) Department of Anatomy I (P. R.), Medizinische Hochschule Hannover, D-30626 Hannover, Germany;(4) Present address: Department of Pediatrics and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 943005;(5) Present address: Ingenium Pharmaceuticals AG, Lochhamer Str. 29, D-82152 Martinsried, Germany |
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Abstract: | 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. |
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Keywords: | c-MYC Clara cells polycystic kidney T-cell lymphomas |
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