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H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation of mitogenic signaling

Item Type:Article
Title:H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation of mitogenic signaling
Creators Name:Nazarenko, I. and Kristiansen, G. and Fonfara, S. and Guenther, R. and Gieseler, C. and Kemmner, W. and Schaefer, R. and Petersen, I. and Sers, C.
Abstract:H-REV107-1, a known member of the class II tumor suppressor gene family, is involved in the regulation of differentiation and survival. We analyzed H-REV107-1 in non-small cell lung carcinomas, in normal lung, and in immortalized and tumor-derived cell lines. Sixty-eight percent of lung tumors revealed positive H-REV107-1-specific staining. Furthermore, survival analysis demonstrated a significant association of cytoplasmic H-REV107-1 with decreased patient survival. This suggested that H-REV107-1, known as a tumor suppressor, plays a different role in non-small cell lung carcinomas. Knock-down of H-REV107-1 expression in lung carcinoma cells inhibited anchorage-dependent and anchorage-independent growth whereas overexpression of H-REV107-1 induced tumor cell proliferation. Consistent with results of the survival analysis, cytoplasmic localization of the protein was essential for this growth-inducing function. Analysis of signaling pathways potentially involved in this process demonstrated that overexpression of H-REV107-1 stimulated RAS-GTPase activity, ERK1,2 phosphorylation, and caveolin-1 expression in the cell lines analyzed. These results indicate that H-REV107-1 is deficient in its function as a tumor suppressor in non-small cell lung carcinomas and is required for proliferation and anchorage-independent growth in cells expressing high levels of the protein, thus contributing to tumor progression in a subset of non-small cell lung carcinomas.
Keywords:Calcium-Independent Phospholipases A2, Cultured Tumor Cells, Enzyme Activation, Immunohistochemistry, Intracellular Membranes, Intracellular Signaling Peptides and Proteins, Lung Neoplasms, Mitogen-Activated Protein Kinase 3, Non-Small-Cell Lung Carcinoma, Prognosis, ras Proteins, Signal Transduction, Small Interfering RNA, Transcriptional Activation, Tumor Suppressor Proteins
Source:American Journal of Pathology
Publisher:American Society for Investigative Pathology
Page Range:1427-1439
Date:October 2006
Official Publication:https://doi.org/10.2353/ajpath.2006.051341
PubMed:View item in PubMed

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