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

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

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalCarcinogenesis
Volume28
Issue number2
DOIs
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Cancer Research

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