Molecular Definition of Breast Tumor Heterogeneity

Michail Shipitsin, Lauren L. Campbell, Pedram Argani, Stanislawa Weremowicz, Noga Bloushtain-Qimron, Jun Yao, Tatiana Nikolskaya, Tatiana Serebryiskaya, Rameen Beroukhim, Min Hu, Marc K. Halushka, Saraswati Sukumar, Leroy M. Parker, Karen S. Anderson, Lyndsay N. Harris, Judy E. Garber, Andrea L. Richardson, Stuart J. Schnitt, Yuri Nikolsky, Rebecca S. GelmanKornelia Polyak

Research output: Contribution to journalArticle

1013 Scopus citations

Abstract

Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-β pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.

Original languageEnglish (US)
Pages (from-to)259-273
Number of pages15
JournalCancer cell
Volume11
Issue number3
DOIs
StatePublished - Mar 13 2007
Externally publishedYes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Shipitsin, M., Campbell, L. L., Argani, P., Weremowicz, S., Bloushtain-Qimron, N., Yao, J., Nikolskaya, T., Serebryiskaya, T., Beroukhim, R., Hu, M., Halushka, M. K., Sukumar, S., Parker, L. M., Anderson, K. S., Harris, L. N., Garber, J. E., Richardson, A. L., Schnitt, S. J., Nikolsky, Y., ... Polyak, K. (2007). Molecular Definition of Breast Tumor Heterogeneity. Cancer cell, 11(3), 259-273. https://doi.org/10.1016/j.ccr.2007.01.013