Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer
| Autor: | Nicole Deutschmann, Christine Sers, Manuela Pacyna-Gengelbach, Waleed F.M. Amin Kotb, H Yasumoto, Iver Petersen, Fei Ye, Karsten Schlüns, T Usui, Yi Chen, Per Lund, Thomas Knösel |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Lung Neoplasms tumour suppressor Tumor suppressor gene medicine.medical_treatment Apoptosis Adenocarcinoma Biology Decitabine Transfection Insulin-like growth factor-binding protein Pathology and Forensic Medicine Cell Line Tumor Internal medicine medicine Humans Lung cancer DNA Modification Methylases Lung Neoplasm Staging DNA methylation human lung cancer Tumor Suppressor Proteins Growth factor Epithelial Cells DNA Neoplasm Methylation Microarray Analysis medicine.disease Immunohistochemistry stable transfection eye diseases IGFBP-rP1 Insulin-Like Growth Factor Binding Proteins Endocrinology Cell culture Azacitidine Carcinoma Squamous Cell Cancer research biology.protein sense organs |
| Zdroj: | The Journal of Pathology. 211:431-438 |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.2132 |
| Popis: | Insulin-like growth binding protein-related protein 1 (IGFBP-rP1) has decreased expression in various tumors, but the role of IGFBP-rP1 in lung cancer has not yet been elucidated. In this study, we evaluated the IGFBP-rP1 expression in lung cancer cell lines and we found a reduced expression of IGFBP-rP1 at both mRNA and protein levels. In a tissue microarray containing 138 primary tumors analyzed by immunohistochemistry, 58 cases (42%) exhibited no expression of IGFBP-rP1, additionally, an association between IGFBP-rP1 expression and tumor gradings was found in squamous cell lung cancer. Neither deletion or gene rearrangement nor loss of heterozigosity was responsible for the inactivation of IGFBP-rP1. However, 5-aza-2'-deoxycytidine treatment restored the expression of IGFBP-rP1 in 3 out of 4 lung cancer cell lines. Sequencing of sodium bisulfite?treated genomic DNA from these 3 lung cancer cell lines revealed a heterogeneous methylation pattern in the region of exon 1 and intron 1. Stable transfection of IGFBP-rP1 full-length cDNA into a lung cancer cell line H2170 led to an increased protein expression of IGFBP-rP1. IGFBP-rP1 positive transfectants remarkably reduced the ability of colony formation in soft agar, suppressed the tumor growth rate in nude mice and increased the number of apoptotic cells as well as the expression level of casepase-3 compared to controls. Moreover, treatment with differentiation modulating agent 5-bromodeoxyuridine (BrdU) led to an enhanced expression of IGFBP-rP1 in lung cancer cells. Out data suggest that IGFBP-rP1 is a tumor suppressor possibly via DNA methylation and induction of apoptosis in human lung cancer. |
| Databáze: | OpenAIRE |
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