Vitamin A and its analogues (
retinoids) regulate the differentiation of epithelial tissues.
Retinoids inhibit the induction of rat
mammary cancers by
carcinogens in vivo, and cellular
binding proteins for
retinoids have been demonstrated in some human
breast cancer samples. In this study, we examined the model system of human
breast cancer cell lines in long-term tissue culture for effects of
retinoids on growth and for the presence of cellular
retinoid binding proteins.
Retinoic acid and
retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines.
Retinoic acid is more potent than
retinol in this regard: 50% growth inhibition is achieved by 6 nM
retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 muM
retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time.
Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of
retinoic acid. Specific and distinct binding of [(3)H]
retinoic acid and [(3)H]
retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by
sucrose density gradient centrifugation. In ZR-75-B, [(3)H]
retinoic acid binding was present, but no binding of [(3)H]
retinol was detectable. This study reveals that
retinoids may play an important role in the regulation and treatment of human
breast cancer and that human
breast cancer cell lines represent a useful model to study this role.