Cell-type-specific responses to chemotherapeutics in breast cancer

Melissa A. Troester, Katherine A. Hoadley, Therese Sørlie, Brittney-Shea Herbert, Anne Lise Børresen-Dale, Per Eystein Lønning, Jerry W. Shay, William K. Kaufmann, Charles M. Perou

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Recent microarray studies have identified distinct subtypes of breast tumors that arise from different cell types and that show statistically significant differences in patient outcome. To gain insight into these differences, we identified in vitro and in vivo changes in gene expression induced by chemotherapeutics. We treated two cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and two lines derived from luminal epithelium (MCF-7 and ZR-75-1) with chemotherapeutics used in the treatment of breast cancer and assayed for changes in gene expression using DNA microarrays. Treatment doses for doxorubicin and 5-fluorouracil were selected to cause comparable cytotoxicity across all four cell lines. The dominant expression response in each of the cell lines was a general stress response; however, distinct expression patterns were observed. Both cell types induced DNA damage-response genes such as p21waf1, but the response in the luminal cells showed higher fold changes and included more p53-regulated genes. Lurninal cell lines repressed a large number of cell cycle-regulated genes and other genes involved in cellular proliferation, whereas the basal cell lines did not. Instead, the basal cell lines repressed genes that were involved in differentiation. These in vitro responses were compared with expression responses in breast tumors sampled before and after treatment with doxorubicin or 5-fluorouracil/mitomycin C. The in vivo data corroborated the cell-type-specific responses to chemotherapeutics observed in vitro, including the induction of p21waf1. Similarities between in vivo and in vitro responses help to identify important response mechanisms to chemotherapeutics.

Original languageEnglish
Pages (from-to)4218-4226
Number of pages9
JournalCancer Research
Volume64
Issue number12
DOIs
StatePublished - Jun 15 2004

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Breast Neoplasms
Cell Line
Fluorouracil
Doxorubicin
Genes
Gene Expression
cdc Genes
p53 Genes
Mitomycin
Human Mammary Glands
Oligonucleotide Array Sequence Analysis
DNA Damage
Therapeutics
Epithelium
Epithelial Cells
Cell Proliferation
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Troester, M. A., Hoadley, K. A., Sørlie, T., Herbert, B-S., Børresen-Dale, A. L., Lønning, P. E., ... Perou, C. M. (2004). Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Research, 64(12), 4218-4226. https://doi.org/10.1158/0008-5472.CAN-04-0107

Cell-type-specific responses to chemotherapeutics in breast cancer. / Troester, Melissa A.; Hoadley, Katherine A.; Sørlie, Therese; Herbert, Brittney-Shea; Børresen-Dale, Anne Lise; Lønning, Per Eystein; Shay, Jerry W.; Kaufmann, William K.; Perou, Charles M.

In: Cancer Research, Vol. 64, No. 12, 15.06.2004, p. 4218-4226.

Research output: Contribution to journalArticle

Troester, MA, Hoadley, KA, Sørlie, T, Herbert, B-S, Børresen-Dale, AL, Lønning, PE, Shay, JW, Kaufmann, WK & Perou, CM 2004, 'Cell-type-specific responses to chemotherapeutics in breast cancer', Cancer Research, vol. 64, no. 12, pp. 4218-4226. https://doi.org/10.1158/0008-5472.CAN-04-0107
Troester MA, Hoadley KA, Sørlie T, Herbert B-S, Børresen-Dale AL, Lønning PE et al. Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Research. 2004 Jun 15;64(12):4218-4226. https://doi.org/10.1158/0008-5472.CAN-04-0107
Troester, Melissa A. ; Hoadley, Katherine A. ; Sørlie, Therese ; Herbert, Brittney-Shea ; Børresen-Dale, Anne Lise ; Lønning, Per Eystein ; Shay, Jerry W. ; Kaufmann, William K. ; Perou, Charles M. / Cell-type-specific responses to chemotherapeutics in breast cancer. In: Cancer Research. 2004 ; Vol. 64, No. 12. pp. 4218-4226.
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