Effect of Ionizing Irradiation on Human Esophageal Cancer Cell Lines by cDNA Microarray Gene Expression Analysis

Abstract

To provide new insights into the molecular mechanisms underlying the effect of irradiation on esophageal squamous cell carcinomas (ESCCs), we used a cDNA microarray screening of more than 4,000 genes with known functions to identify genes involved in the early response to ionizing irradiation. Two human ESCC cell lines, one each of well (TE-1) and poorly (TE-2) differentiated phenotypes were screened. Subconfluent cells of each phenotype were treated with single doses of 2.0 Gy or 8.0 Gy irradiations. After a 15 min incubation time-point, the cells were collected and analyzed. Compared with non-irradiated cells, many genes revealed at least 2-fold upregulation or downregulation at both doses in well or poorly differentiated ESCC cells. The common upregulated genes in well and poorly differentiated cell types at both irradiation doses included SCYA5, CYP51, SMARCD2, COX6C, MAPK8, FOS, UBE2M, RPL6, PDGFRL, TRAF2, TNFAIP6, ITGB4, GSTM3, and SP3 and common downregulated genes involved NFIL3, SMARCA2, CAPZA1, MetAP2, CITED2, DAP3, MGAT2, ATRX, CIAO1, and STAT6. Several of these genes were novel and not previously known to be associated with irradiation. Functional annotations of the modulated genes suggested that at the molecular level, irradiation appears to induce a regularizing balance in ESCC cell function. The genes modulated in the early response to irradiation may be useful in our understanding of the molecular basis of radiotherapy and in developing strategies to augment its effect or establish novel less hazardous alternative adjuvant therapies.

New Frontiers for the NFIL3 bZIP Transcription Factor in Cancer, Metabolism and Beyond

“…Thus, NFIL3 may block the recruitment of bZIP transcriptional activators to pro-apoptotic genes to potentially hinder chemotherapeutic response. In addition to colon cancer, NFIL3 may have a role in esophageal cancer as irradiation of esophageal cancer cell lines leads to a loss in NFIL3 expression 78 . Delineating the full breadth of NFIL3 directed transcriptional programs such as those that counter FOXO and PAR transcription factors will be essential for understanding its contribution to cancer.…”

cDNA microarray analysis of esophageal cancer: discoveries and prospects

“…43 Treatment for 15 min with a single dose of 2.0 Gy or 8.0 Gy was found to induce 24 genes. 44 However, most of the genes identifi ed in these three studies do not overlap.…”

METAP2 (methionyl aminopeptidase 2)

“…Disease Microarray gene expression analysis of human esophageal squamous cell carcinomas revealed that MetAP2 was down-regulated when irradiated (Bo et al, 2004).…”

“…The Src family kinases have been shown to play pivotal roles in cell-cycle progression, making them potential candidates to mediate the cell-cycle effects of MetAP inhibitors. MetAP2 plays a critical role in the proliferation of endothelial cells and certain tumor cells and thus serves as a promising target for antiangiogenesis and anti-cancer drugs (Bo et al, 2004). The inhibition of MetAP2 expression in mesothelioma cells leads to cell death and that such apoptosis is avoided in cases where there is overexpression of Bcl-2 (Catalano et al, 2001).…”