N-(4-hydroxyphenyl)-retinamide selectively increases All-TRANS retinoic acid inhibitory effects in HER2/NEU-overexpressing breast cancer cells.
We previously reported that overexpression of the HER2/NEU oncogene induces all-TRANS retinoic acid (ATRA) resistance in breast cancer cells. N-(4-hydroxyphenyl)-retinamide (4HPR), a synthetic analogue of ATRA, has been shown to repress the expression of HER2/neu and its family member, epidermal growth factor receptor (EGFR). We investigated whether 4HPR, by suppressing HER2/neu or EGFR expression, could sensitize breast cancer cells to ATRA. At 1.3 micro M concentration (a clinically pharmacologically achievable dose), 4HPR increased ATRA sensitivity synergistically in HER2/NEU-overexpressing BT-474, MDA-MB-453, and MCF-7/Her2 breast cancer cells. However, 4HPR did not sensitize EGFR-overexpressing MDA-MB-468, Hs578T, and MCF-7/EGFR breast cancer cells to ATRA. The increased inhibitory effects in HER2/NEU-overexpressing cells were not correlated with increases in expression levels of p21(WAF1/CIP1) or retinoblastoma protein. Combining 4HPR with ATRA may lead to a novel, selective therapeutic or chemopreventive strategy against HER2/NEU-overexpressing breast tumors.
Lim
Soo-Jeong
SJ
Department of Bioimmunotherapy, Section of Immunobiology and Drug Carriers, University of Texas M.D. Anderson Cancer Center, Houston, Tex. 77030, USA.
Gutiérrez-Puente
Yolanda
Y
Tari
Ana M
AM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004357:Drug Synergism; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D016160:Retinoblastoma Protein / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D066246:ErbB Receptors; D017313:Fenretinide; D018719:Erb-b2 Receptor Tyrosine Kinases; D016160:Retinoblastoma Protein; D014212:Tretinoin; C493956:CDKN1A protein, human