Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors

Chad J. Creighton, Kevin E. Cordero, Jose M. Larios, Rebecca S. Miller, Michael D. Johnson, Arul M. Chinnaiyan, Marc E Lippman, James M. Rae

Research output: Contribution to journalArticle

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Abstract

Background: Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors. Results: We generated DNA microarray-based gene expression profiles from three estrogen receptor α (ERα)-positive breast cancer cell lines stimulated by 17β-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. When the patterns of genes regulated by E2 in vitro were compared to those obtained from xenografts, we found a remarkable overlap (over 40%) of genes regulated by E2 in both contexts. These patterns were compared to those obtained from published clinical data sets. We show that, as a group, E2-regulated genes from our preclinical models were co-expressed with ERα in a panel of ERα+ breast tumor mRNA profiles, when corrections were made for patient age, as well as with progesterone receptor. Furthermore, the E2-regulated genes were significantly enriched for transcriptional targets of the myc oncogene and were found to be coordinately expressed with Myc in human tumors. Conclusion: Our results provide significant validation of a widely used in vitro model of estrogen signaling as being pathologically relevant to breast cancers in vivo.

Original languageEnglish
Article numberR28
JournalGenome Biology
Volume7
Issue number4
DOIs
StatePublished - Apr 7 2006
Externally publishedYes

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Heterografts
tumor
breast neoplasms
estrogens
Estrogens
Breast Neoplasms
neoplasms
gene
Estrogen Receptors
Genes
cancer
Neoplasms
genes
Nude Mice
Messenger RNA
myc Genes
oncogenes
MCF-7 Cells
Progesterone Receptors
Oligonucleotide Array Sequence Analysis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Creighton, C. J., Cordero, K. E., Larios, J. M., Miller, R. S., Johnson, M. D., Chinnaiyan, A. M., ... Rae, J. M. (2006). Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors. Genome Biology, 7(4), [R28]. https://doi.org/10.1186/gb-2006-7-4-r28

Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors. / Creighton, Chad J.; Cordero, Kevin E.; Larios, Jose M.; Miller, Rebecca S.; Johnson, Michael D.; Chinnaiyan, Arul M.; Lippman, Marc E; Rae, James M.

In: Genome Biology, Vol. 7, No. 4, R28, 07.04.2006.

Research output: Contribution to journalArticle

Creighton, CJ, Cordero, KE, Larios, JM, Miller, RS, Johnson, MD, Chinnaiyan, AM, Lippman, ME & Rae, JM 2006, 'Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors', Genome Biology, vol. 7, no. 4, R28. https://doi.org/10.1186/gb-2006-7-4-r28
Creighton, Chad J. ; Cordero, Kevin E. ; Larios, Jose M. ; Miller, Rebecca S. ; Johnson, Michael D. ; Chinnaiyan, Arul M. ; Lippman, Marc E ; Rae, James M. / Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors. In: Genome Biology. 2006 ; Vol. 7, No. 4.
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