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Transforming function of the LSM1 oncogene in human breast cancers with the 8p11–12 amplicon

Oncogene volume 26, pages 2104–2114 (2007)Cite this article

Abstract

Amplification of the 8p11–12 region occurs in 15–20% of breast cancers, but the driving oncogene at this locus has yet to be definitively identified. We mapped the 8p11–12 amplicon in breast cancer cell lines and primary human breast cancers and identified the candidate oncogene human Sm-like protein (hLsm1, LSM1) based on increases in copy number and expression level relative to human mammary epithelial cells. To examine the oncogenic role of LSM1, we overexpressed this gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44 breast cancer cell line, which has a natural amplification and overexpression of LSM1. Our data confirmed that LSM1 is an oncogene from the 8p11–12 amplicon by showing that hLsm1 overexpression induced growth factor-independent proliferation and soft agar colony formation in MCF10A cells, and hLsm1 inhibition in SUM44 cells dramatically reduced soft agar growth. Little is known about hLsm1 function other than its involvement in mRNA degradation; therefore, we used expression microarray analysis to investigate how hLsm1 affects cell transformation in MCF10A and SUM44 cells. We identified numerous genes altered following hLsm1 overexpression common to SUM44 breast cancer cells that play important roles in cell cycle regulation, cell proliferation and other cancer-promoting processes. Future work will continue to characterize these important changes to achieve a more complete understanding of the mechanism of hLsm1's effect on cancer progression.

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Acknowledgements

This work was supported by a grant from the National Cancer Institute (RO1 CA100724). Microarray experiments and analysis were performed by the Applied Genomics Technology Center at Wayne State University, which is funded by the Cancer Center Support Grant (P30 CA022453-25). Funding for Dr Sorin Draghici was provided by the following grants: NSF DBI-0234806, NIH R01 HG003491, NIH(NCRR) 1S10 RR01785701, NIH R21 CA10074001, 1R21 EB0099001 and 1R01NS04520701.

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Authors and Affiliations

  1. Breast Cancer Program, Karmanos Cancer Institute, Detroit, MI, USA

    K L Streicher, Z Q Yang & S P Ethier

  2. Department of Computer Science, Wayne State University,

    S Draghici

  3. Bioinformatics Core Leader, Karmanos Cancer Institute, Detroit, MI, USA

    S Draghici

  4. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA

    Z Q Yang & S P Ethier

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  1. K L Streicher
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Correspondence to K L Streicher.

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Streicher, K., Yang, Z., Draghici, S. et al. Transforming function of the LSM1 oncogene in human breast cancers with the 8p11–12 amplicon. Oncogene 26, 2104–2114 (2007). https://doi.org/10.1038/sj.onc.1210002

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