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Alterations in cellular retinol metabolism contribute to differential retinoid responsiveness in normal human mammary epithelial cells versus breast cancer cells.

Abstract：

:The present study was undertaken to compare ROH growth responsiveness between normal human mammary epithelial cells (HMECs), estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cells, and assess whether this responsiveness is correlated with differences in ROH metabolism, particularly RA synthesis. HMECs were markedly more growth sensitive to a physiological dose of ROH than breast cancer cells, exhibiting a significant decrease in cell number by 48h and >70% decrease by 144h. In comparison, numbers of MCF-7s were only decreased 32% by 144h. MDA-MB-231 cells were not affected. However, HMECs and MCF-7 cells displayed similar growth responsiveness to 1 microM RA, while MDA-MB-231 cells were minimally affected. Although the initial rates and extent of ROH uptake were comparable among cell types, ROH levels in HMECs progressively decreased to 20% of the peak by 24h and < or = 10% by 72h. In contrast, ROH levels in the cancer cells remained relatively constant through 48 h. The decrease in HMEC ROH was attributable to greater metabolism as evidenced by rapid and predominant retinyl ester formation. HMECs also produced approximately 5 times more RA from ROH than MCF-7s and approximately 10 times more than MDA MB-231 cells. Our results demonstrate that normal HMECs are markedly more responsive to the growth inhibitory effects of ROH than breast cancer cells, and that this responsiveness is associated with greater ROH metabolism including greater RA synthesis. These data suggest that altered ROH metabolism may be a factor in breast cancer progression.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Hayden LJ,Satre MA

doi

10.1023/a:1014815112078

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

95-105

issue

2

eissn

0167-6806

issn

1573-7217

journal_volume

72

pub_type

杂志文章

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