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

Abstract:

BACKGROUND:There is little effective therapy for patients with hormone-refractory breast cancer. Hormone resistance is frequently due to the transcriptional inactivation of the estrogen receptor (ER) gene. We determined the effect of DHAC, a cytosine DNA methyltransferase (CMT) inhibitor, on the estrogen sensitivity in three human breast carcinoma cell lines with intermediate to low levels of estrogen receptor (ER) expression: MCF7 (adriamycin-sensitive), MCF7M/Adr (adriamycin-resistant), and MDA-435, and one ER+ cell line, 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 estrogen 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 response 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 inhibitors may have a clinical application in treating estrogen-refractory breast cancer patients by restoring the estrogen sensitivity and allowing these patients to respond again to conventional therapy with estrogen antagonists.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Izbicka E,Davidson KK,Lawrence RA,MacDonald JR,Von Hoff DD

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

1293-8

issue

2A

eissn

0250-7005

issn

1791-7530

journal_volume

19

pub_type

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