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 gro...

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Bibliographic Details
Published in:Tumor biology 2002-09, Vol.23 (5), p.279-286
Main Authors: Lim, Soo-Jeong, Gutiérrez-Puente, Yolanda, Tari, Ana M.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - analysis
Drug Synergism
Female
Fenretinide - pharmacology
General aspects
Hematologic and hematopoietic diseases
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Pharmacology. Drug treatments
Receptor, Epidermal Growth Factor - analysis
Receptor, ErbB-2 - analysis
Research Article
Retinoblastoma Protein - analysis
Tretinoin - pharmacology
Tumor Cells, Cultured
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Summary: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 µM 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.
ISSN:1010-4283
1423-0380
DOI:10.1159/000068567