![]() ![]() Functional genomic approaches comparing expression among cell lines and tumor tissue may promote a better understanding of the genes expressed by malignant and host cells during tumor progression and metastasis. Comparison of cell lines and tumor tissue revealed a concordance of ∼50% by array, and 70% for Northern-confirmed, metastasis-related genes. The results demonstrate that early response genes related to NF-κB contribute to metastatic tumor progression. The NF-κB-inducible cytokine Gro-1 was recently shown to promote tumor growth, metastasis, and angiogenesis of squamous cell carcinomas in vivo (Loukinova et al., Oncogene, 19: 3477–3486, 2000). Strikingly, 10 of 22 genes in the cluster expressed in metastases have been associated with activation of the nuclear factor (NF)-κB signal pathway. Alterations in the expression of several genes detected during tumor progression were consistent with their functional activities involving growth ( p21, p27, and cyclin D1), resistance and apoptosis ( glutathione-S-transferase, cIAP-1, PEA-15, and Fas ligand), inflammation and angiogenesis, and signal transduction ( c-Met, yes-associated protein, and syk). Clustering analysis of DD and array results from transformed and metastatic cells identified genes that exhibited decreased or increased expression with transformation and metastasis. cDNA array detected 76.9% of the differentially expressed mRNAs selected from DD and confirmed by Northern blot, whereas low-abundance mRNAs did not reach the threshold for detection by the lower-sensitivity array method. mRNA expression profiles were also generated using a mouse cDNA array composed of 4000 elements representing known genes and expressed sequence tags plus the 57 DD candidate cDNAs detected by Northern analysis to facilitate data validation. Fifty-seven were detected, and 32 were confirmed to be differentially expressed by Northern blot analysis. After DD, 72 candidate cDNAs expressed primarily in transformed and metastatic cells were selected and cloned. We used mRNA differential display (DD) to detect global differences and cDNA arrays enriched for cancer-associated genes using mRNA from primary keratinocytes, transformed Pam 212 squamous carcinoma cells, and metastases of Pam 212. ![]() To identify changes in gene expression with transformation and metastasis, we investigated differential gene expression in a squamous carcinoma model established in syngeneic mice. ![]()
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