Expression of
metallothionein (MT)
isoforms by a human
breast cancer cell line, PMC42, which retains many characteristics of normal breast epithelial cells and expresses functional
estrogen receptors, was examined because it has been proposed that human
breast cancer cells which are
estrogen receptor positive can be differentiated from those which are
estrogen receptor negative, by failure to express MT-1E [J.A. Friedline, S.H. Garrett, S. Somji, J.H. Todd, D. A. Sens, Differential expression of the MT-1E gene in
estrogen-receptor positive and -negative
breast cancer cell lines, Am. J. Pathol. 152 (1998) 23-27]. Using RT-PCR, PMC42 cells were found to transcribe genes for the MT
isoforms IE, IX and 2A but not 1A or 1H. In order to examine which of the expressed
isoforms might protect against
metal toxicity, the cells were challenged with high concentrations of
zinc and
copper. Using competitive RT-PCR, cells resistant to 500 microM
zinc showed 7+/-2 fold (SD, n=3) increases in expression of
MT-1X and 6+/-3 fold increases in expression of MT-2A compared to control cells in normal media. For cells resistant to 250 microM
copper the corresponding increases were 37+/-13 and 60+/-20 fold, whilst for control cells treated with 250 microM
copper for only 6 h, increases were 10+/-3 and 6+/-3 fold. There was only a low level of expression of MT-1E in untreated cells and but a >120 fold increase in
copper- resistant cells. Thus
estrogen receptor positive cells cannot, in general, be differentiated from
estrogen receptor negative cells by failure to express MT-1E, as suggested by Friedline et al. (1998). Increased expression of MT-1E, as well as
MT-1X and MT-2A, protects against
metal toxicity in PMC42
breast cancer cells.