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  • Title: Induction of adipocyte-specific gene expression is correlated with mammary tumor regression by the retinoid X receptor-ligand LGD1069 (targretin).
    Author: Agarwal VR, Bischoff ED, Hermann T, Lamph WW.
    Journal: Cancer Res; 2000 Nov 01; 60(21):6033-8. PubMed ID: 11085524.
    Abstract:
    Targretin (LGD1069; a high-affinity ligand for the retinoid X receptors) is an efficacious chemotherapeutic and chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary carcinoma model. To evaluate the molecular action of LGD1069 in mammary carcinoma we have examined gene expression patterns in controls and nonresponding tumors compared with tumors undergoing regression (responding) by LGD1069. When compared with controls or nonresponding tumors, the expression of adipocyte-related genes such as adipocyte P2 (aP2), adipsin, peroxisome proliferator-activated receptor gamma (PPARgamma), and lipoprotein lipase was elevated in LGD1069-responding tumors. Further analysis showed that gene expression changes occurred rapidly, in as little as 6 h, after the first dose of LGD1069. Immunohistochemical analysis showed that aP2 protein was also highly expressed in responding tumors when compared with control or nonresponding tumors. More importantly, aP2 protein was localized in the tumor cells in addition to the adipocytes present in the tumors. Similar changes in gene expression and inhibition in growth were seen in tumor cells (cloned from N-nitroso-N-methylurea-induced carcinoma) exposed to LGD1069 in vitro. These data suggest that tumor regression by LGD1069 involves differentiation induction along the adipocyte lineage.
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