Search for Genes Involved in UV-Resistance in Human Cells by mRNA Differential Display: Increased Transcriptional Expression of Nucleophosmin and T-Plastin Genes in Association with the Resistance

Higuchi, Yoshinori; Kita, K; Nakanishi, Hiroshi; Wang, Xiaoli; Sugaya, Shigeru; Tanzawa, Hideki; Yamamori, Hideo; Sugita, Katsuo; Yamaura, Akira; Suzuki, Nobuo

doi:10.1006/bbrc.1998.8978

Cited by 42 publications

(28 citation statements)

References 19 publications

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“…Moreover, transfecting these cells with NPM antisense mRNA led to a decrease in cell survival after UV irradiation. 38 Posttranslational modifications of NPM were also observed after exposure to ionizing radiation: treatment of SQ20B cells with radiation results in increased expression of an ADP-ribosylated and phosphorylated species of NPM. 39 If the first study clearly demonstrated the involvement of the long form of NPM in UV resistance, the posttranslational modifications observed after irradiation in the second work should occur either on NPM or on NPM2.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of a COOH‐truncated nucleophosmin resulting from alternative splicing is associated with cellular resistance to ionizing radiation in HeLa cells

Drouet

Ader

Delmas

et al. 2002

Intl Journal of Cancer

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We previously demonstrated that transfecting HeLa cells with the 24 kDa basic fibroblast growth factor-2 (FGF-2) isoform dramatically increased cell survival after irradiation. To investigate genes implicated in this radioresistance acquisition, we compared mRNA expression between radioresistant 24 kDa FGF-2-expressing cells (HeLa 3A) and radiosensitive control HeLa PINA cells using the differential display technique. Of the 32 differentially expressed mRNAs, 1 presented a significant homology with a known gene. This 378 bp fragment presented 100% identity with exon 11 and 12 of human nucleophosmin (NPM) but differed by including a part of intron 9 in its 5ℙ end. The differential expression of this fragment was confirmed using an RNase protection assay. We then cloned the entire corresponding mRNA and showed that it contained all the exons of NPM plus intron 9, suggesting that it was a splicing product of the NPM gene. This variant encoded for a 35-amino acid truncated NPM (NPM2). NPM2 expression was increased in HeLa 3A. To investigate NPM2's role in radioresistance acquisition, we transfected HeLa cells with NPM2 cDNA and analyzed survival after irradiation of the clones obtained. After transfection with NPM2, radiosensitive HeLa cells exhibited a dramatic increase in cell survival after irradiation. Taken together, our results demonstrate that expression of a COOH-truncated NPM form resulting from the alternative splicing of NPM mRNA is able to increase cell survival after irradiation and suggests that it might be involved in cellular response to ionizing radiation.

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Section: Discussionmentioning

confidence: 99%

Increased expression of a COOH‐truncated nucleophosmin resulting from alternative splicing is associated with cellular resistance to ionizing radiation in HeLa cells

Drouet

Ader

Delmas

et al. 2002

Intl Journal of Cancer

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“…NPM/B23 has also been shown to be transcriptionally down-regulated during retinoic acid-induced cellular differentiation (Hsu and Yung, 1998) and sodium butyrate-induced apoptosis (Liu and Yung, 1998). Moreover, overexpression of NPM/B23 makes cells resistant to UV-induced growth inhibition and cell death (Higuchi et al, 1998;Wu et al, 2002). These observations suggest that NPM/B23 is involved in the regulation of cellular differentiation and apoptosis; increased expression of NPM/B23 may have a protective role in differentiation and apoptosis, hence sensitize cells to cellular transformation.…”

Section: Npm/b23 In the Cell Cycle Control And In Cellular Transformamentioning

confidence: 99%

The role of nucleophosmin in centrosome duplication

2002

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“…NPM is a major nuclear matrix protein whose expression is associated with an increased resistance to UV-induced cell death (Higuchi et al, 1998). Overexpression of NPM has been described in several leukemic cell lines and NPM is capable of inducing transformation of NIH3T3 cells (Kondo et al, 1997).…”

Section: Transcriptional Regulators Involved In Aml-associated Fusionmentioning

confidence: 99%

Common themes in the pathogenesis of acute myeloid leukemia

et al. 2001

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The pathogenesis of acute myeloid leukemia is associated with the appearance of oncogenic fusion proteins generated as a consequence of speci®c chromosome translocations. Of the two components of each fusion protein, one is generally a transcription factor, whereas the other partner is more variable in function, but often involved in the control of cell survival and apoptosis. As a consequence, AML-associated fusion proteins function as aberrant transcriptional regulators that interfere with the process of myeloid di erentiation, determine a stagespeci®c arrest of maturation and enhance cell survival in a cell-type speci®c manner. The abnormal regulation of transcriptional networks occurs through common mechanisms that include recruitment of aberrant corepressor complexes, alterations in chromatin remodeling, and disruption of speci®c subnuclear compartments. The identi®cation and analysis of common and speci®c target genes regulated by AML fusion proteins will be of fundamental importance for the full understanding of acute myeloid leukemogenesis and for the implementation of disease-speci®c drug design. Oncogene (2001) 20, 5680 ± 5694.

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Search for Genes Involved in UV-Resistance in Human Cells by mRNA Differential Display: Increased Transcriptional Expression of Nucleophosmin and T-Plastin Genes in Association with the Resistance

Cited by 42 publications

References 19 publications

Increased expression of a COOH‐truncated nucleophosmin resulting from alternative splicing is associated with cellular resistance to ionizing radiation in HeLa cells

Increased expression of a COOH‐truncated nucleophosmin resulting from alternative splicing is associated with cellular resistance to ionizing radiation in HeLa cells

The role of nucleophosmin in centrosome duplication

Common themes in the pathogenesis of acute myeloid leukemia

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