EB1089, a vitamin D receptor agonist, reduces proliferation and decreases tumor growth rate in a mouse model of hormone-induced mammary cancer.
1,25-Dihydroxyvitamin D3 and several of its analogs, such as EB1089, induce growth arrest and apoptosis of breast cancer cells in culture. EB1089 has also been shown to limit growth of xenografts in nude mice and carcinogen-induced mammary tumors in rats. Coupled with the fact that the vitamin D receptor is highly expressed in a large proportion of breast tumors, these data suggest that it may be a broad spectrum therapeutic target. We utilized a transgenic model of hormone-induced mammary cancer, the LH-overexpressing mouse, to assess, for the first time, the efficacy of EB1089 in a spontaneous tumor model. Similar to human breast cancers, the pre-neoplastic mammary glands and mammary tumors in these mice express high levels of vitamin D receptor. Treatment with EB1089 decreased proliferation of mammary epithelial cells in pre-neoplastic glands by 35%. Moreover, half of hormone-induced mammary tumors treated with EB1089 demonstrated a decreased rate of growth, with a subset of these tumors even regressing, suggesting that 1,25-dihydroxyvitamin D3 analogs may be effective chemopreventive and chemotherapeutic agents for breast cancer.
Milliken
Erin L
EL
Department of Pharmacology, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
Zhang
Xiaoxue
X
Flask
Chris
C
Duerk
Jeffrey L
JL
MacDonald
Paul N
PN
Keri
Ruth A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000188:drug therapy*; D018167:Receptors, Calcitriol / Q000819:agonists*
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D007986:Luteinizing Hormone; D002117:Calcitriol; C078903:seocalcitol