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Clin Cancer Res. 2006 May 15;12(10):3010-8.

17Beta-estradiol induces down-regulation of Cap43/NDRG1/Drg-1, a putative differentiation-related and metastasis suppressor gene, in human breast cancer cells.

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  • 1Center for Innovative Cancer Therapy of the 21st Century Center of Excellence Program for Medical Science and Departments of Surgery and Pathology, Kurume University, Kurume, Fukuoka, Japan.



Cap43 is known as a nickel- and calcium-inducible gene. In the present study, we examined whether 17beta-estradiol (E2) could affect the expression of Cap43 in breast cancer.


Real-time PCR, immunoblotting, and immunocytochemistry were used to examine the expression of Cap43 and estrogen receptor-alpha (ER-alpha) in breast cancer cell lines. MDA-MB-231 and SK-BR-3 cell lines were transfected with ER-alpha cDNA to establish cells overexpressing ER-alpha. Immunohistochemistry was used to evaluate the expression of the Cap43 protein in breast cancer patients (n = 96), and the relationship between Cap43 expression and clinicopathologic findings was examined.


Of the eight cell lines, four expressed higher levels of Cap43 with very low levels of ER-alpha, whereas the other four expressed lower levels of Cap43 with high ER-alpha levels. Treatment with E2 decreased the expression of Cap43 dose-dependently in ER-alpha-positive cell lines but not in ER-alpha-negative lines. Administration of antiestrogens, tamoxifen and ICI 182780, abrogated the E2-induced down-regulation of Cap43. Overexpression of ER-alpha in both ER-alpha-negative cell lines, SK-BR-3 and MDA-MB-231, resulted in down-regulation of Cap43. Immunostaining studies showed a significant correlation between Cap43 expression and the histologic grade of tumors (P = 0.0387). Furthermore, Cap43 expression was inversely correlated with the expression of ER-alpha (P = 0.0374).


E2-induced down-regulation of Cap43 seems to be mediated through ER-alpha-dependent pathways in breast cancer cells both in culture and in patients. Cap43 has potential as a molecular marker to determine the therapeutic efficacy of antiestrogenic anticancer agents in breast cancer.

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