Abstract
The Ras-CRK-Rap1 cellular signal-transduction system is regulated by guanine nucleotide exchange factors (GEFs). Transcription of C3G on chromosome 9q34 and a key member of the GEF gene family is activated by the CRK-adaptor protein; the C3G product is a CRK SH3 domain-binding guanine nucleotide-releasing factor. We document here the amplification of C3G in five of 18 primary non-small cell lung cancers examined and its increased expression in 18 of 28 tumors in comparison to corresponding non-cancerous lung tissues. Immunohistochemical staining revealed prominent C3G protein in the cytoplasm of cancer cells, associated with faint staining at the nucleolar membrane, but C3G was not detectable in normal bronchial mucoepithelial cells or in broncholoalveolar cells of the bronchial/bronchiolar ducts or alveoli. These data indicate that amplification and increased expression of the C3G gene may play some role in human lung carcinogenesis through derangement of the CRK-Rap1 signaling pathway.
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Acknowledgements
The authors thank Aya Yabe, Sizuyo Miyamoto, Junko Sato, Mayumi Tanaka, and Naoko Tsuruta for their technical assistance. This work was supported by special grants for Strategic Advanced Research on “Cancer” from the Ministry of Education, Science, Sports and Culture of Japan; by a Research Grant from the Ministry of Health and Welfare of Japan; and by a Research for the Future Program Grant of The Japan Society for the Promotion of Science.
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Hirata, T., Nagai, H., Koizumi, K. et al. Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers. J Hum Genet 49, 290–295 (2004). https://doi.org/10.1007/s10038-004-0148-1
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DOI: https://doi.org/10.1007/s10038-004-0148-1
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