The interaction between ER and NFκB in resistance to endocrine therapy

Breast Cancer Research

Table 2 Mechanisms of endocrine resistance

Influencing factor	Mechanism	Examples
Growth factors and kinases	Influence on post-translational modifications of ER and its co-regulatory proteins, and influence on nongenomic ER activity	EGFR/HER2, IGF1-R, FGFR, MAPK, PI3K
Cofactors	Determine whether selective ER modulators act as agonist or antagonist and affect the ligand-independent activity of ER	AIB1, NCOR1
Genes regulated by ER	Interact with ERα and affect the level of hormone receptors and deregulate the cell cycle	HSP90, FKBPL
Transcription factors	Stimulate progression to estrogen independent tumor growth or modulate ER activity	ERβ, AP1, NFκB
Genetic abnormalities	Mutations in cytochrome p450 prevent tamoxifen to be converted to its active metabolite endoxifen	CYP450, ER

AIB1, amplified in breast 1; AP1, activator protein 1; CYP450, cytochrome p450; EGFR, epidermal growth factor receptor; ER, estrogen receptor; FGFR, fibroblast growth factor receptor; FKBPL, FK506-binding protein like; HSP90, heat shock protein 90; IGF1-R, insulin-like growth factor-1 receptor; MAPK, mitogen-activated protein kinase; NCOR1, co-repressor of estrogen receptor; PI3K, phosphatidylinositol-3 kinase.

ISSN: 1465-542X