Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer

Ryung S. Kim, Alvaro Avivar-Valderas, Yeriel Estrada, Paloma Bragado, Maria Soledad Sosa, Julio A. Aguirre-Ghiso, Jeffrey E. Segall

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Breast cancers can recur after removal of the primary tumor and treatment to eliminate remaining tumor cells. Recurrence may occur after long periods of time during which there are no clinical symptoms. Tumor cell dormancy may explain these prolonged periods of asymptomatic residual disease and treatment resistance. We generated a dormancy gene signature from published experimental models and applied it to both breast cancer cell line expression data as well as four published clinical studies of primary breast cancers. We found that estrogen receptor (ER) positive breast cell lines and primary tumors have significantly higher dormancy signature scores (P<0.0000001) than ER- cell lines and tumors. In addition, a stratified analysis combining all ER+ tumors in four studies indicated 2.1 times higher hazard of recurrence among patients whose tumors had low dormancy scores (LDS) compared to those whose tumors had high dormancy scores (HDS) (p<0.000005). The trend was shown in all four individual studies. Suppression of two dormancy genes, BHLHE41 and NR2F1, resulted in increased in vivo growth of ER positive MCF7 cells. The patient data analysis suggests that disseminated ER positive tumor cells carrying a dormancy signature are more likely to undergo prolonged dormancy before resuming metastatic growth. Furthermore, genes identified with this approach might provide insight into the mechanisms of dormancy onset and maintenance as well as dormancy models using human breast cancer cell lines.

Original languageEnglish (US)
Article numbere35569
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 18 2012

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metastasis
Estrogen Receptors
breast neoplasms
dormancy
Tumors
Breast Neoplasms
Neoplasm Metastasis
Cells
Neoplasms
neoplasms
cell lines
Tumor Cell Line
Genes
Asymptomatic Diseases
Recurrence
Cell Line
Disease Resistance
MCF-7 Cells
Growth
estrogen receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. / Kim, Ryung S.; Avivar-Valderas, Alvaro; Estrada, Yeriel; Bragado, Paloma; Sosa, Maria Soledad; Aguirre-Ghiso, Julio A.; Segall, Jeffrey E.

In: PLoS One, Vol. 7, No. 4, e35569, 18.04.2012.

Research output: Contribution to journalArticle

Kim, RS, Avivar-Valderas, A, Estrada, Y, Bragado, P, Sosa, MS, Aguirre-Ghiso, JA & Segall, JE 2012, 'Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer', PLoS One, vol. 7, no. 4, e35569. https://doi.org/10.1371/journal.pone.0035569
Kim RS, Avivar-Valderas A, Estrada Y, Bragado P, Sosa MS, Aguirre-Ghiso JA et al. Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. PLoS One. 2012 Apr 18;7(4). e35569. https://doi.org/10.1371/journal.pone.0035569
Kim, Ryung S. ; Avivar-Valderas, Alvaro ; Estrada, Yeriel ; Bragado, Paloma ; Sosa, Maria Soledad ; Aguirre-Ghiso, Julio A. ; Segall, Jeffrey E. / Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. In: PLoS One. 2012 ; Vol. 7, No. 4.
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