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RET receptor tyrosine kinase isoforms in kidney function and disease

Oncogene volume 21, pages 5582–5592 (2002)Cite this article

Abstract

The RET proto-oncogene encodes two major isoforms, RET9 and RET51, which differ at the carboxyl-terminal. Loss-of-function mutations in RET result in gut aganglionosis while gain of function mutations result in cancer syndromes. From studies on transgenic mice, RET9 is important for early development of the kidney and the enteric nervous system. Little is known about the function of RET isoforms in later life. Here we report the expression of RET isoforms and its signalling complex, GDNF and GFRα1, in foetal and adult human kidneys. We found their expression in both the developing and the adult renal collecting system. We further show that only RET51 but not RET9 could promote the survival and tubulogenesis of mIMCD3 (mouse inner medullary collecting duct) cells in collagen gel. Our results agree with the hypothesis that RET51 signalling is related to differentiation events in later kidney organogenesis. In addition, it may also have a function in the adult kidney. We further extend our study by showing increased RET and GDNF expression in collecting duct cysts of polycystic kidney patients. This suggests that GDNF/RET signalling may contribute to proliferation of the collecting duct epithelium in an autocrine/paracrine manner.

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Acknowledgements

We thank Vassilis Pachnis for providing plasmids and comments, Lucy O'Brien for collagen gel culture technique, Vincent Lui for GFRα1 plasmid, WL Wong and Rebecca Lee for technical assistance. This work was supported by CRCG Grants, the University of Hong Kong to SY Chan.

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Authors and Affiliations

  1. Department of Paediatrics and Centre of Human Development and Birth Defects, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

    Davy Chun Wai Lee & Siu Yuen Chan

  2. Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

    Kwok Wah Chan

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  1. Davy Chun Wai Lee
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Correspondence to Siu Yuen Chan.

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Lee, D., Chan, K. & Chan, S. RET receptor tyrosine kinase isoforms in kidney function and disease. Oncogene 21, 5582–5592 (2002). https://doi.org/10.1038/sj.onc.1205741

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