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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

Authors: Hideki Makinoshima, Genichiro Ishii, Motohiro Kojima, Satoshi Fujii, Youichi Higuchi, Takeshi Kuwata, Atsushi Ochiai

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease.

Methods

We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines.

Results

Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model.

Conclusion

PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs.
Appendix
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Metadata
Title
PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma
Authors
Hideki Makinoshima
Genichiro Ishii
Motohiro Kojima
Satoshi Fujii
Youichi Higuchi
Takeshi Kuwata
Atsushi Ochiai
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-537

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