Cell lines from the same cervical carcinomabut with different radiosensitivities exhibit different cDNA microarray patterns of gene expression

Abstract

Combining chemotherapy with radiotherapy has improved the cure rate among patients with cancers of the cervix. Although one-half to two-thirds of the patients can be cured by radiation alone, such patients cannot be identified at present and must therefore suffer the burden of chemotherapy. Our long-range goal is to identify those cervical cancers that are radiosensitive and could be cured by radiotherapy alone. The advent of methods that permit the simultaneous analysis of expression patterns of thousands of genes, make it feasible to attempt to identify the molecular events related to radiosensitivity and the associated regulatory pathways. We hypothesize that the sensitivity of tumor cells to ionizing radiation (IR) is determined by the level of expression of specific genes that may be identified with the aid of cDNA microarrays. As the first step in testing this hypothesis, we determined the gene expression differences between two cell lines exhibiting different degrees of radiosensitivity. These were derived from the same tumor prior to treatment from a patient with squamous cell carcinoma of the cervix. The mRNA from these cells was subjected to cDNA analysis on a microarray of 5,776 known genes and ESTs. The expression of 52 genes of the total of 5,776 was elevated (maximum 4.1 fold) in the radioresistant cells as compared to the radiosensitive cells. Ten of the 52 sequences are known genes while 42 are ESTs. Conversely, the expression of 18 genes was elevated in the sensitive cells as compared to the resistant cells. Seven of these 18 are known genes while eleven are ESTs. Among the genes expressed differentially between the resistant and sensitive cells were several known to be associated with response to IR and many more genes and ESTs that had not previously been reported to be related to radiosensitivity. The genes that showed the greatest overexpression in the radioresistant cell line were metal-regulatory transcription factor-1, cytochrome P450 CYP1B1, adenomatosis polyposis coli, translation elongation factor-1, cytochrome-c oxidase, whereas in the sensitive cell line, transcription factor NF-kappa-B, metalloproteinase inhibitor-1 precursor, superoxide dismutase-2, insulin-like growth factor binding protein-3, guanine nucleotide-binding protein and transforming growth factor beta-induced protein were overexpressed.

CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study

“…cytochrome CYP1B1 showed the greatest overexpression in radioresistant cell lines (7). at low patient numbers, the results did not reveal a modified risk in former uranium miners in terms of CYP1A1 or CYP1B1 polymorphisms and smoking status.…”

Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma

“…The relationship between cytochrome c oxidase and chemo or radioresistance has been reported in various tumor cell lines (15)(16)(17)(18)(19). Comprehensive gene analysis on a microarray in cervical carcinoma cells (squamous cell carcinoma) showed that MT-CO1 was increased by a factor greater than two in RRCs compared with radiosensitive cells (15).…”

“…Comprehensive gene analysis on a microarray in cervical carcinoma cells (squamous cell carcinoma) showed that MT-CO1 was increased by a factor greater than two in RRCs compared with radiosensitive cells (15). Also, in human acute myelogenic leukemia cells, MT-CO3 was upregulated in chemoresistant cells compared with in chemosensitive cells (16).…”

Genetic Effects of X-Ray and Carbon Ion Irradiation in Head and Neck Carcinoma Cell Lines

“…The success or Carbon Ion-Enhanced Genes in Oral Cancer failure of radiotherapy can be affected by the radiosensitivity of the tumor target and the limits imposed on treatment by the radiosensitivity of normal tissues. Recently, several studies using microarrays technique have successfully identified and classified a set of human genes that are radiosensitive to X-ray irradiation 1,8,10,12,18,32) . Modern curative radiotherapy requires higher doses to tumors and minimal irradiation to the surrounding normal tissues.…”