Growth factor receptor cross-talk with estrogen receptor as a mechanism for tamoxifen resistance in breast cancer.
Breast cancer growth is regulated by steroid hormones and by polypeptide hormones and growth factors. Endocrine therapies for breast cancer have been designed to interrupt estrogen signaling by either blocking its receptor (ER) or by lowering the amount of estrogen available in the cell for binding. These therapies are very effective in many patients but de novo and acquired resistance are common. Growing evidence suggests that cross-talk between ER and growth factor receptor pathways contributes to the development of this resistance. Signaling via the EGF receptor and HER-2/neu can activate both ER and the important ER coactivator AIB1. In turn, ER located in the cell membrane can activate the growth factor receptor pathways. Breast tumors with high levels of AIB1 and HER-2 may be resistant to tamoxifen because of an increase in its estrogen agonist activity.
Osborne
C Kent
CK
Breast Center, Baylor College of Medicine and The Methodist Hospital, One Baylor Plaza, BCM 600, Houston, TX 77030, USA.
Schiff
Rachel
R
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D020239:Receptor Cross-Talk / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013629:Tamoxifen / Q000627:therapeutic use; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D013629:Tamoxifen; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1