Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer

Cancer Res. 2012 Jan 1;72(1):220-9. doi: 10.1158/0008-5472.CAN-11-1976. Epub 2011 Nov 9.


The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence of a hormone-independent tumor. The steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In this discovery study, we identified ADAM22, a non-protease member of the ADAM family of disintegrins, as a direct estrogen receptor (ER)-independent target of SRC-1. We confirmed SRC-1 as a regulator of ADAM22 by molecular, cellular, and in vivo studies. ADAM22 functioned in cellular migration and differentiation, and its levels were increased in endocrine resistant-tumors compared with endocrine-sensitive tumors in mouse xenograft models of human breast cancer. Clinically, ADAM22 was found to serve as an independent predictor of poor disease-free survival. Taken together, our findings suggest that SRC-1 switches steroid-responsive tumors to a steroid-resistant state in which the SRC-1 target gene ADAM22 has a critical role, suggesting this molecule as a prognostic and therapeutic drug target that could help improve the treatment of endocrine-resistant breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / physiology*
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nerve Tissue Proteins / physiology*
  • Nuclear Receptor Coactivator 1 / genetics*
  • Receptors, Estrogen / metabolism*
  • Transcriptome*


  • Antineoplastic Agents, Hormonal
  • Nerve Tissue Proteins
  • Receptors, Estrogen
  • Nuclear Receptor Coactivator 1
  • ADAM Proteins
  • ADAM22 protein, human