TAMOXIFEN INHIBITS GROWTH OF ESTROGEN RECEPTOR-NEGATIVE A549 CELLS

The non-steroidal anti-oestrogen tamoxifen inhibits proliferation of t he A549 human lung adenocarcinoma cell line (EC(50)similar or equal to 10 nM) yet there was no evidence of oestrogen receptor expression as determined by ligand binding assay and northern blotting. 17-beta-Oest radiol had no effect on A549 cell proliferation (1 pM-1 mu M) and more over a 100-fold excess failed to reverse the effect of 10 nM tamoxifen as did a 100-fold excess of the steroidal anti-oestrogens ICI 164384 and ICI 182780. However, 4-hydroxytamoxifen which had no significant e ffect on A549 cell growth (1 pM-1 mu M) completely antagonized the eff ect of 10nM tamoxifen when used at a 100-fold excess. In the presence of oleic acid and stearic acid (10 mu M) the growth inhibitory effect of tamoxifen in A549 cells was greatly enhanced, unlike effects mediat ed by the anti-oestrogen binding protein described in other cells wher e these fatty acids had no effect. These results indicate the presence of a unique and highly sensitive mechanism in A549 cells whereby conc entrations of tamoxifen relevant to classical receptor binding can inh ibit cell growth in the absence of the oestrogen receptor.