Expression profile of microRNAs in c-Myc induced mouse mammary tumors
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c-Myc is a transcription factor overexpression of which induces mammary cancer in transgenic mice. To explore whether certain microRNAs (mirRNA) mediate c-Myc induced mammary carcinogenesis, we studied mirRNA expression profile in mammary tumors developed from MMTV-c-myc transgenic mice, and found 50 and 59 mirRNAs showing increased and decreased expression, respectively, compared with lactating mammary glands of wild type mice. Twenty-four of these mirRNAs could be grouped into eight clusters because they had the same chromosomal localizations and might be processed from the same primary RNA transcripts. The increased expression of mir-20a, mir-20b, and mir-9 as well as decreased expression of mir-222 were verified by RT-PCR, real-time RT-PCR, and cDNA sequencing. Moreover, we fortuitously identified a novel non-coding RNA, the level of which was decreased in proliferating mammary glands of MMTV-c-myc mice was further decreased to undetectable level in the mammary tumors. Sequencing of this novel RNA revealed that it was transcribed from a region of mouse chromosome 19 that harbored the metastasis associated lung adenocarcinoma transcript-1 (Malat-1), a non-protein-coding gene. These results suggest that certain mirRNAs and the chromosome 19 derived non-coding RNAs may mediate c-myc induced mammary carcinogenesis.
Keywordsc-myc MicroRNA Breast cancer Microarray
This work is supported by a grant from Elsa U. Pardee Foundation on microRNA in breast cancer and a grant from NCI, NIH (RO1CA100864) to D.J. Liao. We would like to thank Dr. Fred Bogott for his excellent English editing of the manuscript.
- 20.Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, O’brien-Jenkins A, Katsaros D, Hatzigeorgiou A, Gimotty PA, Weber BL, Coukos G et al (2006) MicroRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci USA 103:9136–9141. doi: 10.1073/pnas.0508889103 CrossRefPubMedGoogle Scholar
- 29.Sabbir MG, Roy A, Mandal S, Dam A, Roychoudhury S, Panda CK (2006) Deletion mapping of chromosome 13q in head and neck squamous cell carcinoma in Indian patients: correlation with prognosis of the tumour. Int J Exp Pathol 87:151–161. doi: 10.1111/j.0959-9673.2006.00467.x CrossRefPubMedGoogle Scholar
- 48.Timmer T, Terpstra P, van den BA, Veldhuis PM, Ter EA, van der Veen AY, Kok K, Naylor SL, Buys CH (1999) An evolutionary rearrangement of the Xp11.3–11.23 region in 3p21.3, a region frequently deleted in a variety of cancers. Genomics 60:238–240. doi: 10.1006/geno.1999.5878 CrossRefPubMedGoogle Scholar
- 56.Suzuki A, Shibata T, Shimada Y, Murakami Y, Horii A, Shiratori K et al (2008) Identification of SMURF1 as a possible target for 7q21.3–22.1 amplification detected in a pancreatic cancer cell line by in-house array-based comparative genomic hybridization. Cancer Sci 99:986–994. doi: 10.1111/j.1349-7006.2008.00779.x CrossRefPubMedGoogle Scholar
- 57.Law FB, Chen YW, Wong KY, Ying J, Tao Q, Langford C et al (2007) Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma. Oncogene 26:5877–5888. doi: 10.1038/sj.onc.1210390 CrossRefPubMedGoogle Scholar
- 62.Pettenati MJ, Le Beau MM, Lemons RS, Shima EA, Kawasaki ES, Larson RA et al (1987) Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Proc Natl Acad Sci USA 84:2970–2974. doi: 10.1073/pnas.84.9.2970 CrossRefPubMedGoogle Scholar
- 64.Shipley JM, Birdsall S, Clark J, Crew J, Gill S, Linehan M et al (1995) Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case. Cytogenet Cell Genet 71:280–284. doi: 10.1159/000134127 CrossRefPubMedGoogle Scholar