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PMID: 15356345 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 38 ·2004-09-21 ·Pages 13844-9

Motiwala T, Kutay H, Ghoshal K, Bai S, Seimiya H, Tsuruo T, Suster S, Morrison C, Jacob ST

Abstract

Previous study in our laboratory demonstrated suppression of the gene for protein tyrosine phosphatase receptor-type O (PTPRO) in primary and established rat hepatomas. The present study showed methylation-mediated silencing of this gene in primary human lung tumors and in several human lung cancer cell lines, one of the characteristics of many tumor-suppressor genes. The reduced expression of PTPRO in the primary lung tumors correlated with the methylation status of its CpG island. Demethylation of the gene by deoxy-5-azacytidine treatment led to its reactivation in a lung cancer line (A549). Overexpression of PTPRO in A549 cells inhibited anchorage-independent growth, delayed reentry of the cells into the cell cycle after release from cell-cycle arrest, and increased susceptibility of the cells to apoptosis. These data have demonstrated the growth-suppressor characteristics of PTPRO that are unique to a classical tumor suppressor.

MeSH Terms
Base Sequence Cell Line, Tumor DNA Primers Gene Expression Regulation, Neoplastic/genetics Gene Silencing/physiology Genes, Tumor Suppressor Genetic Vectors Humans Lung Neoplasms/genetics Protein Tyrosine Phosphatases/genetics Receptor-Like Protein Tyrosine Phosphatases, Class 2 Transfection
Chemicals
DNA Primers PTPRU protein, human Protein Tyrosine Phosphatases Ptpru protein, rat Receptor-Like Protein Tyrosine Phosphatases, Class 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Motiwala Tasneem
Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Kutay Huban
Ghoshal Kalpana
Bai Shoumei
Seimiya Hiroyuki
Tsuruo Takashi
Suster Saul
Morrison Carl
Jacob Samson T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0405451101
Published
2004-09-21
Epub
2004-00-08
Pages
13844-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC518843
Subset
IM
Grants
NCI NIH HHS · R01 CA086978 · United States
NIEHS NIH HHS · ES 10874 · United States
NCI NIH HHS · CA 86978 · United States
NIEHS NIH HHS · R01 ES010874 · United States
NCI NIH HHS · R01 CA081024 · United States
NCI NIH HHS · CA 81024 · United States
External Links
PubMed source DOI: 10.1073/pnas.0405451101 PMC Full Text View journal details
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