Transforming function of the LSM1 oncogene in human breast cancers with the 8p11-12 amplicon.
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.
Streicher
K L
KL
Breast Cancer Program, Karmanos Cancer Institute, Detroit, MI 48201, USA. streiche@karmanos.org
Yang
Z Q
ZQ
Draghici
S
S
Ethier
S P
SP
D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D017077:Culture Media, Conditioned; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*
D017077:Culture Media, Conditioned; C464824:LSM1 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D007334:Insulin-Like Growth Factor I