Table 1.
Nuclear Receptor | Expression in Breast Cancer | NR Activation—Phenotypes
|
||
---|---|---|---|---|
Proliferation | Apoptosis | Relevance to Breast Cancer Therapy | ||
Steroid Hormone Receptors | ||||
ER-α | Overexpression common ∼70% | Proproliferative | Antiapoptotic | Expression determines utility of therapy with SERM or AI (3) |
ER-β | Not routinely assessed; likely low | Antiproliferative | Unknown | Increased expression may be a favorable marker (27,28) |
PR-A | Expression frequent with ER-α | Proproliferative | Antiapoptotic | May be regulated by ER-α and reflect Tam sensitivity (50) |
PR-B | Not routinely assessed | Unknown | Unknown | High PR-A:PR-B ratio increases relapse risk with Tam Rx (48) |
AR | Overepression ∼48%–78% | Antiproliferative | Unknown | Appears to be favorable when expressed (48) |
GR-α | Overexpression ∼50% | Antiproliferative | Antiapoptotic | Unknown |
Coregulators | ||||
AIB1/SRC-3 | Overexpression (amplification) | Proproliferative | Unknown | High expression may promote Tam resistance (38) |
N-CoR | Variable | Antiprolferative | Unknown | Low N-Cor is associated with shorter relapse-free survival (38) |
PPARs | ||||
PPAR-α | Unknown | Proproliferative | Unknown | Unknown |
PPAR-β/δ | Unknown | Proproliferative | Antiapoptotic | Unknown |
PPAR-γ | Overexpression | Antiproliferative | Proapoptotic | Increased PPAR-γ expression correlates with survival (83) |
RAR and RXR | ||||
RAR-α | Variable | Antiproliferative | Unknown | The synthetic RAR ligand, fenritinide, reduces second breast cancers in premenopausal women (111) |
RAR-β | Down-regulated | Antiproliferative | Unknown | |
RAR-γ | Variable | Antiproliferative | Unknown | Unknown |
RXRs | Variable | Antiproliferative | Proapoptotic | Unknown |
VDR | ||||
VDR | Variable | Antiproliferative | Proapoptotic | Vitamin D and calcium intake may inversely correlate with the risk of breast cancer in women (103) |
Orphan Receptors (ERRs) | ||||
ERR-α | Overexpression | Proproliferative | Unknown | Correlated with overexpression of Her2 and poor prognosis (126) |
ERR-β | Overexpression | Unknown | Unknown | |
ERR-γ | Overexpression | Proproliferative | Unknown | Correlated with hormonally responsive ER/PR positivity (125) |
Tam, Tamoxifen; Rx, therapy.