Differences in metallothionein expression in transplantable mouse mammary tumor lines

In order to elucidate a possible role of metallothionein (MT) in mammary carcinogenesis, MT and sex hormone receptor (estrogen receptor, ER; progesterone receptor, PR) expressions were investigated immunohistochemically in a transplantable pregnancy-dependent mouse mammary tumor (TPDMT-4) and related autonomous tumor sublines (T4-OI96, T4-OI165 and T4-OI320CY) recovered from pregnant and virgin DDD mice. TPDMT-4 showed MT expression in tumor cells, while the expression was less evident in T4-OI165 and T4-OI96 among the autonomous tumor lines; in T4-OI320CY, the MT expression was similar to that in TPDMT-4. Chromatographic study of MT contents in the tumor lines confirmed the results of the immunohistochemical examination. PR and ER were localized in the tumor cells of TPDMT-4, but not in those of autonomous tumor sublines. In TPDMT-4, a significant correlation was observed between MT and ER expressions (r=0.83, P<0.01), but not between MT and PR expressions (r=0.26, P>0.4), also between MT expression and mitotic activity (r=−0.34, P>0.3). Since T4-OI96 and T4-OI165 are known to be more malignant than T4-OI320CY, the present study indicates a negative correlation between the MT positivity and progression of the transplantable mammary tumor in mice.