Summary The effects of the major human serum bile acid, glycochenodeoxycholic acid (GCDC), as well as unconjugated chenodeoxycholic acid (CDC), on the MCF-7 human breast cancer cell line have been studied in vitro under oestrogen and bile acid deprived culture conditions. GCDC increased the growth of the breast cancer cells over the range 10-300 jiM. At concentrations in excess of the bile acid binding capacity of the medium cell growth was prevented. In contrast 10 jiM CDC tended to reduce cell growth. Oestrogen (ER) and progesterone (PgR) receptors, pS2 and total cathepsin D were quantified by monoclonal antibody based immunoassays. Ten to 100 jiM GCDC and 10 jIM CDC down-regulated ER protein and this was accompanied by induction of the oestrogen-regulated proteins PgR, pS2 and possibly cathepsin D, including increased secretion of the latter two proteins into the culture medium. All these changes were quantitatively similar to those observed with 10 nm oestradiol. The bile acid effects on ER and PgR were not due to interference with the assay procedures. Cells incubated with 50 jIM GCDC or 10 jIM CDC had higher pmolar concentrations of the bile acids than controls. This study suggests that naturally occurring bile acids influence the growth and steroid receptor function of human breast cancer cells.Although bile acids have been considered to play a role in the aetiology and/or growth of colorectal cancer (Hill, 1983) little attention has been paid to the possible activity of these steroidal compounds in breast cancer. Epidemiological studies have demonstrated that rates of breast and colon cancers are highly correlated with each other and with high fat and animal protein diets (Drasar & Irving, 1973). In the few studies published the data suggest that women with breast cancer may have differences in the faecal excretion of bile acids compared with controls; decreased (Murray et al., 1980) and increased (Papatestas et al., 1982) faecal concentrations, and altered ratio of individual bile acids (Owen et al., 1986) have been reported. Long-term follow-up of women undergoing cholecystectomy has revealed an increased risk of breast cancer which increased with time after operation (Gudmundsson et al., 1989). In contrast, by reducing the enterohepatic circulation of oestrogens and bile acids, the high consumption of fibre and fermented milk products, particularly in combination with low fat and animal protein intake, may provide some protection against breast cancer (Adlercreutz, 1990). These findings, while by no means conclusive, imply that breast cancer patients are subject to changes in circulating levels of bile acids and consequently the potential exposure of breast tissue and/or tumour. In support of the latter possibility is our observation, now confirmed by others, that breast cyst fluid contains very high levels of bile acids, notably the glycine conjugates of chenodeoxycholic (CDC), deoxycholic and cholic acids (Baker et al., 1986 and1988a;Raju et al., 1990).Bile acids have been shown to produce DNA chan...
