Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer.
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.
Motiwala
Tasneem
T
Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Kutay
Huban
H
Ghoshal
Kalpana
K
Bai
Shoumei
S
Seimiya
Hiroyuki
H
Tsuruo
Takashi
T
Suster
Saul
S
Morrison
Carl
C
Jacob
Samson T
ST
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D014162:Transfection
D017931:DNA Primers; C516868:PTPRU protein, human; D017027:Protein Tyrosine Phosphatases; C516870:Ptpru protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2