5,6-dihydro-5 '-azacytidine (DHAC) affects estrogen sensitivity in estrogen-refractory human breast carcinoma cell lines

Citation
E. Izbicka et al., 5,6-dihydro-5 '-azacytidine (DHAC) affects estrogen sensitivity in estrogen-refractory human breast carcinoma cell lines, ANTICANC R, 19(2A), 1999, pp. 1293-1298
Citations number
19
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ANTICANCER RESEARCH
ISSN journal
02507005 → ACNP
Volume
19
Issue
2A
Year of publication
1999
Pages
1293 - 1298
Database
ISI
SICI code
0250-7005(199903/04)19:2A<1293:5'(AES>2.0.ZU;2-C
Abstract
Background; There is litde effective therapy for patients with hormone-refr actory breast cancer. Hormone resistance is frequently due to the transcrip tional inactivation of the estrogen receptor (ER) gene. We,determined the e ffect of DHAC, a cytosine DNA methyltransferase (CMT) inhibitor, on the est rogen sensitivity in three human breast carcinoma cell lines with intermedi ate to low levels of estrogen receptor (EB) expression: MCF7 (adriamycin-se nsitive), MCF7M/Adr (adriamycin-resistant), and MDA-435, and one ER+ cell l ine ZR75-1. Materials and Methods: Cells maintained in culture were exposed to DHAC or vehicle continuously for 14 days, then exposed to estradiol or tamoxifen and counted on day 21. Results: Exposure to DHAC did not affect e strogen sensitivity in ZR-75-1 and MCF7M/Adr cells. DHAC treatment of MCF7 and MDA-435 cells resulted in significant (p<0.05) growth stimulation in re sponse to estrogen at 10(-6) M, and to growth modulation by tamoxifen at 10 (-5) to 10(-7) M. Conclusions: These data suggest that DHAC can restore the estrogen sensitivity in ER-breast cancer. Thus, DHAC and other novel CMT i nhibitors may have a clinical application in treating estrogen-refractory b reast cancer patients by restoring the estrogen sensitivity and allowing th ese patients to respond again to conventional therapy with estrogen antagon ists.