The retinoid X receptor-selective retinoid, LGD1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice.
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.
Wu
Kendall
K
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Zhang
Yun
Y
Xu
Xiao-Chun
XC
Hill
Jamal
J
Celestino
Joseph
J
Kim
Hee-Tae
HT
Mohsin
Syed K
SK
Hilsenbeck
Susan G
SG
Lamph
William W
WW
Bissonette
Reid
R
Brown
Powel H
PH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000077610:Bexarotene; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018734:Genes, erbB-2; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D008822:Mice, Transgenic; D011960:Receptors, Estrogen / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D019076:Transgenes / Q000187:drug effects / Q000235:genetics
D016588:Anticarcinogenic Agents; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D000077610:Bexarotene