The retinoid X receptor-selective retinoid, LGD1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 22; pp. 6376 - 6380
• Main Authors: WU, Kendall, YUN ZHANG, BROWN, Powel H, XU, Xiao-Chun, HILL, Jamal, CELESTINO, Joseph, KIM, Hee-Tae, MOHSIN, Syed K, HILSENBECK, Susan G, LAMPH, William W, BISSONETTE, Reid
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-11-2002
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Division - drug effects; Chemical agents; Female; Gene Expression - drug effects; Genes, erbB-2; Mammary Glands, Animal - cytology; Mammary Glands, Animal - drug effects; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Mammary Tumor Virus, Mouse; Medical sciences; Mice; Mice, Transgenic; Receptors, Estrogen - physiology; Receptors, Retinoic Acid - metabolism; Retinoid X Receptors; Tetrahydronaphthalenes - pharmacology; Transcription Factors - metabolism; Transgenes - drug effects; Transgenes - genetics; Tumors; Estrogen receptor; Rodentia; Retinoid; Transgenic animal; Selectivity; Malignant tumor; Anticarcinogen; Gene expression; Carcinogenesis; Prevention; Mammary gland diseases; Vertebrata; Chemotherapy; Mammalia; Mouse; Animal; RXR retinoid receptor; Mammary gland
• ISSN: 0008-5472; 1538-7445

Despite the effectiveness of the selective estrogen receptor (ER) modulators in preventing ER-positive breast cancer, chemopreventive agents still need to be developed for the prevention of ER-negative breast cancers. The naturally occurring retinoids are promising agents for the prevention of human cancers but are too toxic for long-term chronic use. We previously demonstrated that the chemopreventive effects of the retinoids could be separated from the toxicity by using an RXR-selective retinoid, LGD1069. The studies described here demonstrate that LGD1069 effectively suppresses ER-negative tumor development in mouse mammary tumor virus-erbB2 transgenic mice with minimal toxicity. These studies suggest that receptor-selective retinoids are promising agents for the prevention of breast cancer and that they may be particularly useful in preventing ER-negative breast cancer.