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 journalArticle

42 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Breast Neoplasms
Growth
Down Syndrome
Chromosomes, Human, Pair 21
Inborn Genetic Diseases
Gene Dosage
Metalloproteases
Tumor Suppressor Genes
Intellectual Disability
Inhibition (Psychology)
Organism Cloning
Breast
Transcription Factors
Down-Regulation
Neoplasm Metastasis
Cell Line
Population

ASJC Scopus subject areas

  • Cancer Research

Cite this

Kwak, H. I., Gustafson, T., Metz, R. P., Laffin, B., Schedin, P., & Porter, W. W. (2007). Inhibition of breast cancer growth and invasion by single-minded 2s. Carcinogenesis, 28(2), 259-266. https://doi.org/10.1093/carcin/bgl122

Inhibition of breast cancer growth and invasion by single-minded 2s. / Kwak, Hyeong Il; Gustafson, Tanya; Metz, Richard P.; Laffin, Brian; Schedin, Pepper; Porter, Weston W.

In: Carcinogenesis, Vol. 28, No. 2, 02.2007, p. 259-266.

Research output: Contribution to journalArticle

Kwak, HI, Gustafson, T, Metz, RP, Laffin, B, Schedin, P & Porter, WW 2007, 'Inhibition of breast cancer growth and invasion by single-minded 2s', Carcinogenesis, vol. 28, no. 2, pp. 259-266. https://doi.org/10.1093/carcin/bgl122
Kwak, Hyeong Il ; Gustafson, Tanya ; Metz, Richard P. ; Laffin, Brian ; Schedin, Pepper ; Porter, Weston W. / Inhibition of breast cancer growth and invasion by single-minded 2s. In: Carcinogenesis. 2007 ; Vol. 28, No. 2. pp. 259-266.
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