Characterization of transformation related genes in oral cancer cells

Chang, David D.; Park, No‐Hee; Denny, Christopher T.; Nelson, Stanley F.; Pe, Mark

doi:10.1038/sj.onc.1201715

Cited by 54 publications

(49 citation statements)

References 21 publications

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“…expressed genes as reported previously (Zhang et al, 1997;Chang et al, 1998). Thus, we conclude that the cDNA fragments obtained in this study represent a signi®cant fraction of genes dierentially regulated in the two phenotypically normal REF52 and 208F cell lines.…”

Section: Resultssupporting

confidence: 52%

Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

et al. 1999

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The signal-transducing Ras proteins are important driving forces of diverse cellular processes such as proliferation, neoplastic transformation, dierentiation and growth inhibition. As a step toward understanding the complex mechanisms underlying cellular responses, gene expression patterns were examined in two phenotypically normal ®broblast lines which dier in their sensitivity toward oncogene-mediated transformation. Suppression subtractive hybridization (SSH) was used to establish a subtracted cDNA library speci®c for the REF52 cell line which, like normal diploid ®broblasts, is refractory toward neoplastic transformation induced by mutated HRAS oncogenes. In contrast, rat 208F control cells can be eciently transformed by HRAS. The nucleotide sequence of 549 subtracted cDNA clones (`REF52 minus 208F') was determined. We identi®ed 93 preferentially expressed gene fragments in resistant REF52 cells as compared to 208F cells. Seventeen of the 52 known genes (32.6%) are capable of inhibiting cell proliferation or of adversely aecting oncogenic signal transduction pathways. These results suggest that the anti-oncogenic properties of resistant REF52 cells are determined by multiple negative growth regulators. The preneoplastic state expressed in 208F cells is characterized by impairment of unexpectedly redundant control mechanisms. Our results also demonstrate that SSH is a powerful method for identifying speci®c transcriptional patterns in closely related cell types.

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Section: Resultssupporting

confidence: 52%

Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

et al. 1999

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“…Development of the quantitative real-time RT ± PCR method for the determination of relative changes in gene expression o ers the added advantage of expanding this approach beyond simple pair-wise comparisons (Heid et al, 1996). The application of cDNA array hybridization as a high-throughput screening method for di erential gene expression has been applied to develop a more comprehensive picture of pathways associated with genotoxic stress (Amundson et al, 1999) and to characterize transformation related genes in oral cancer cells (Chang et al, 1998) and in ®broblasts (Tchernitsa et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1

et al. 2000

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“…DISCUSSION A cDNA array hybridization approach as a high throughput screening method for differential gene expression has been applied to develop a comprehensive picture of pathways linked to proteasome inhibition (3). Similar approaches were taken to characterize genotoxic stress patterns (28), transformationrelated genes in oral cancer cells (29) and fibroblasts (30), and early steps in immortalization of Burkitt lymphoma (31), to name just a few.…”

Section: Erk3 Protects Cells From the Antiproliferative Effect Of Promentioning

confidence: 99%

Proteasome- and p38-dependent Regulation of ERK3 Expression

Zimmermann

Lamerant

Grossenbacher

et al. 2001

Journal of Biological Chemistry

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Proteasome inhibition leads to accumulation of transcription factors, heat shock proteins, cyclins, and other proteasome substrate proteins by blocking their proteolytic degradation. An increase in gene transcription upon proteasome inhibition was found for a group of proteins, including p21 WAF1/CIP1 , ubiquitin, and transcription factors. In this study, we have demonstrated selective up-regulation of extracellular signal-regulated kinase 3 (ERK3) mRNA and protein expression upon treatment with peptide-based proteasome inhibitors or lactacystin. ERK3 is a family member of the mitogenactivated protein kinases (also called ERK) that are key mediators of signal transduction from the cell surface to the nucleus. ERK3 up-regulation is independent of the p53, Bcl2, and caspase 3 status of cells. p38 pathway kinase inhibitors prevent proteasome-dependent ERK3 induction and enhance the antiproliferative effect of proteasome inhibitors. MCF-7 cells expressing ERK3 ectopically show increased resistance toward proteasome inhibition. The results indicate that ERK3 expression is a consequence of p38 pathway activation and most probably represents an intracellular defense or rescue mechanism against cell stress and damage induced by proteasome inhibition.Proteasome inhibition leads to an increase in the expression of a large number of proteins by both posttranslational and transcriptional mechanisms. Various proteins crucial for cell cycle regulation and stress response, such as cyclins and transcription factors, are substrates of the ubiquitin-proteasome proteolytic pathway and directly accumulate in a polyubiquitinylated state after proteasome inhibitor treatment. On the other hand, proteasome inhibition has been reported to increase transcription and translation of a group of genes, including p21 WAF1/CIP1 (1), and a number of proteins involved in heat shock response (2) and transcriptional regulation, such as Gadd153, ATF3, and MAD1 (3).As reported previously, we have used a quantitative fluorescent cDNA hybridization approach to identify genes regulated transcriptionally in response to proteasome inhibitor treatment. Changes in mRNA expression of 7900 genes from the UniGene collection were compared upon exposure of cells to the proteasome inhibitors lactacystin, lactacystin-␤-lactone, or MG132 by means of microarray-based cDNA hybridization (3). All these inhibitors block the proteolytic activity of the 26 S proteasome without influencing its ATPase or isopeptidase activities. The three gene expression profiles were very similar, revealing 52 genes that are induced more than 5-fold and 34 genes that are repressed more than 5-fold by at least one of the inhibitors.A gene raising interest and found to be up-regulated on all three cDNA array chips was ERK3, a MAP 1 kinase of the extracellular signal-regulated kinase (ERK) subfamily. MAP kinases are serine/threonine kinases that are phosphorylated and thereby activated in response to a wide array of stimuli and are part of sequentially acting complex protein kinase cascades...

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Characterization of transformation related genes in oral cancer cells

Cited by 54 publications

References 21 publications

Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1

Proteasome- and p38-dependent Regulation of ERK3 Expression

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