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Expulsion of micronuclei containing amplified genes contributes to a decrease in double minute chromosomes from malignant tumor cells.

ABSTRACT: Double minute chromosomes (DMs) are a hallmark of gene amplification. The relationship between the formation of DMs and the amplification of DM-carried genes remains to be clarified. The human colorectal cancer cell line NCI-H716 and human malignant primitive neuroectodermal tumor cell line SK-PN-DW are known to contain many DMs. To examine the amplification of DM-carried genes in tumor cells, we performed Affymetrix SNP Array 6.0 analyses and verified the regions of amplification in NCI-H716 and SK-PN-DW tumor cells. We identified the amplification regions and the DM-carried genes that were amplified and overexpressed in tumor cells. Using RNA interference, we downregulated seven DM-carried genes, (NDUFB9, MTSS1, NSMCE2, TRIB1, FAM84B, MYC and FGFR2) individually and then investigated the formation of DMs, the amplification of the DM-carried genes, DNA damage and the physiological function of these genes. We found that suppressing the expression of DM-carried genes led to a decrease in the number of DMs and reduced the amplification of the DM-carried genes through the micronuclei expulsion of DMs from the tumor cells. We further detected an increase in the number of γH2AX foci in the knockdown cells, which provides a strong link between DNA damage and the loss of DMs. In addition, the loss of DMs and the reduced amplification and expression of the DM-carried genes resulted in a decrease in cell proliferation and invasion ability.

SUBMITTER: Ji W

PROVIDER: S-EPMC4233979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Constitutive ERK1/2 activation contributes to production of double minute chromosomes in tumour cells.

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Chromosomes trapped in micronuclei are liable to segregation errors.

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Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression.

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| S-EPMC5302943 | biostudies-literature

Micronuclei from misaligned chromosomes that satisfy the spindle assembly checkpoint in cancer cells.

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