| X-linked Gene Expression Profiles by RNAi-Mediated BRCA1 Knockdown in MCF7 Cells. |
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Min Ae Song, Jung Hoon Park, Hee Jeong Ahn, Jung Jae Ko, Suman Lee |
1Functional Genomics Lab, Bundang Campus, Pochon CHA University College of Medicine, Sungnam-Si, Gyeonggi-Do 463-836, Korea.
2CHA Research Institute, Bundang Campus, Pochon CHA University College of Medicine, Sungnam-Si, Gyeonggi-Do 463-836, Korea.
3Department of Pathology, Bundang CHA Hospital, Pochon CHA University College of Medicine, Sungnam-Si, Gyeonggi-Do 463-836, Korea. |
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| Abstract |
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Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF 7 breast cancer cell line.
The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF 7 cells after BRCA1 knockdown.
The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1%) and 12 downregulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells. |
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