Journal Article

Inhibition of breast cancer growth and invasion by single-minded 2s

Hyeong-Il Kwak, Tanya Gustafson, Richard P. Metz, Brian Laffin, Pepper Schedin and Weston W. Porter

in Carcinogenesis

Volume 28, issue 2, pages 259-266
Published in print July 2006 | ISSN: 0143-3334
Published online February 2007 | e-ISSN: 1460-2180 | DOI:
Inhibition of breast cancer growth and invasion by single-minded 2s

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  • Clinical Cytogenetics and Molecular Genetics


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Single-minded 2 (SIM2) is a member of the bHLH-PAS family of transcription factors. SIM2 was initially identified by positional cloning on chromosome 21 and is thought to contribute to the etiology of trisomy-21 [Down syndrome (DS)]. In addition to the physical and mental deficiencies associated with this genetic disease, it has become apparent that women with DS are 10–25times less likely to die from breast cancer in comparison with age-matched normal populations. This is thought to be a result of gene dosage effect of tumor suppressor genes on chromosome 21. Here, we report that a splice variant of SIM2, SIM2 short (SIM2s), is differentially expressed in normal breast and breast cancer-derived cell lines and is downregulated in human breast cancer samples. Re-establishment of SIM2s in MDA-MB-435 breast cancer cells significantly reduced proliferation, anchorage-independent growth and invasive potential. Consistent with its role as a transcriptional repressor, SIM2s directly decreased expression of matrix metalloprotease-3, a known mediator of breast cancer metastasis. These results suggest that SIM2s has breast tumor suppressive activity.

Journal Article.  5810 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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