Human breast cancer cells and normal mammary epithelial cells: retinol metabolism and growth inhibition by the retinol metabolite 4-oxoretinol.

Abstract

To understand the signaling and growth-inhibitory effects of retinoids, we have examined the metabolism of [3H]retinol in a number of estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) human breast cancer cell lines. We have also assayed the metabolism of [3H]retinol in normal human mammary epithelial cells. The ER+ breast cancer cell lines MCF-7 and T47D produce [3H]4-oxoretinol from [3H]retinol; the production of [3H]4-oxoretinol is increased by initial culture in the presence of nonradiolabeled retinoic acid (RA) or N-(4-hydroxyphenyl)retinamide, indicating that these drugs enhance [3H]retinol metabolism to [3H]4-oxoretinol. No metabolism of [3H]retinol to [3H]RA in these ER+ tumor lines was detected. ER- breast cancer lines MDA-MB-231, MDA-MB-468, and BT20 do not metabolize [3H]retinol to [3H]4-oxoretinol. In the ER- tumor lines, most of the [3H]retinol remains unmetabolized during the 24-h culture period; MDA-MB-468 and BT20 metabolize some [3H]retinol to [3H]RA. Unlike the majority of the tumor lines, the normal human breast epithelial cell strains AD074 and MCF10A rapidly metabolize [3H]retinol to [3H]retinyl esters. No detectable [3H]RA is produced from [3H]retinol in AD074 and MCF10A cells. Thus, the normal breast epithelial strains, the ER+ tumor lines and the ER- tumor lines differ greatly in their pathways of [3H]retinol metabolism. The levels of cellular retinol binding protein-I mRNA expression are not correlated with the levels or types of various retinol metabolites. Whereas the normal breast epithelial cells and the ER+ tumor lines are growth inhibited by RA, N-(4-hydroxyphenyl)retinamide, and 4-oxoretinol, only the 4-oxoretinol is growth inhibitory in the ER- tumor lines. The cellular retinoic acid-binding protein II mRNA levels are not correlated with the growth inhibition by RA or 4-oxoretinol in the normal and tumor lines.

• Authors: A C Chen, X Guo, F Derguini, L J Gudas
• Journal: Cancer research (Cancer Res) Vol. 57 Issue 20 Pg. 4642-51 (Oct 15 1997) ISSN: 0008-5472 [Print] United States
• PMID: 9377581 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RBP1 protein, human
• RBP2 protein, human
• RNA, Messenger
• Retinol-Binding Proteins
• Retinol-Binding Proteins, Cellular
• Tritium
• Vitamin A
• 4-oxoretinol

Topics

• Breast (cytology)
• Breast Neoplasms (metabolism)
• Cell Division (drug effects)
• Cell Line
• Chromatography, High Pressure Liquid
• Epithelial Cells (cytology, drug effects, metabolism)
• Female
• Humans
• Kinetics
• RNA, Messenger (biosynthesis)
• Retinol-Binding Proteins (biosynthesis)
• Retinol-Binding Proteins, Cellular
• Transcription, Genetic
• Tritium
• Tumor Cells, Cultured
• Vitamin A (analogs & derivatives, metabolism, pharmacology)