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

• Published in: Oncogene Vol. 26; no. 14; pp. 2104 - 2114
• Main Authors: Streicher, K L, Yang, Z Q, Draghici, S, Ethier, S P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.03.2007; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Cell Biology; Cell cycle; Cell Line, Tumor; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - genetics; Chromosomes, Human, Pair 8 - genetics; Copy number; Culture Media, Conditioned; DNA microarrays; Epithelial cells; Female; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gene Dosage; Gene expression; Gene Expression Profiling; Genetic aspects; Gynecology. Andrology. Obstetrics; Human Genetics; Human subjects; Humans; Identification and classification; Insulin-Like Growth Factor I - metabolism; Internal Medicine; Mammary gland; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Methods; Molecular and cellular biology; mRNA; Oncogenes; Oncology; original-article; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; RNA, Small Interfering - pharmacology; RNA-Binding Proteins - antagonists & inhibitors; RNA-Binding Proteins - genetics; Tumor cell lines; Tumors; United States; LSM1; chromosome 8p11–12; breast cancer; Human; Mammary gland diseases; chromosome 8p11-12; Chromosome 12; Breast cancer; Malignant tumor; Onc gene; Carcinogenesis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210002

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.