Abstract: |
Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1-a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage. ©2006 American Association for Cancer Research. |
Keywords: |
signal transduction; controlled study; human tissue; promoter region; squamous cell carcinoma; carcinoma, squamous cell; nonhuman; genetic analysis; animal cell; mouse; animals; mice; cell survival; gene targeting; gene overexpression; apoptosis; gene amplification; neoplasm proteins; sonic hedgehog protein; animal experiment; animal model; hedgehog proteins; rna, small interfering; in vivo study; cancer cell culture; in vitro study; cell line, tumor; mice, inbred balb c; transcription factors; cell transformation, neoplastic; oncogenes; molecular cloning; cloning, molecular; oncogene; gene activation; gene expression regulation, neoplastic; recombinant fusion proteins; mice, nude; cell transformation; oncogene proteins; fibroblast; gene control; neoplasm transplantation; transcription factor gli1; short hairpin rna; genetic conservation; nih 3t3 cells; chromosome 3q; chromosomes, human, pair 3; squamous cell carcinoma related oncogene
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