NDLI: Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer

Content Provider	PubMed Central
Author	Yee, Nelson S. Zhou, Weiqiang Liang, I-chau
Copyright Year	2011
Abstract	Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7) gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg2+ partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a) gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg2+ rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg2+-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis.
Related Links	http://dx.doi.org/10.1242/dmm.004564
Ending Page	254
Page Count	15
Starting Page	240
File Format	PDF
ISSN	17548403
e-ISSN	17548411
Journal	Disease Models & Mechanisms
Issue Number	2
Volume Number	4
Language	English
Publisher	The Company of Biologists Limited
Publisher Date	2011-03-01
Access Restriction	Open
Rights Holder	The Company of Biologists Limited
Subject Keyword	Immunology and Microbiology (miscellaneous) Biochemistry, Genetics and Molecular Biology(all) Medicine (miscellaneous) Neuroscience (miscellaneous) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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