Metallothioneins (MTs) belong to a family of
cysteine-rich,
metal-binding intracellular
proteins, which have been linked with cell proliferation. In this study, expression levels of the 8 known MT-1 and MT-2 functional
isoforms in human invasive ductal
breast cancer specimens were determined by RT-PCR. The expression profiles of the MT
protein and MT-2A
mRNA were further evaluated in 79 cases of human invasive ductal
breast carcinoma by immunohistochemistry and in situ hybridization, and correlated with
cancer cell proliferation (determined by Ki-67
nuclear antigen immunolabeling). MT-1A, MT-1E, MT-1F, MT-1G, MT-1H,
MT-1X and MT-2A but not MT-1B, were detected in
breast cancer tissue samples. The MT-2A
mRNA transcript was the highest among all the
isoforms detected. A positive correlation was observed between MT-2A
mRNA and MT
protein expression with Ki-67 labeling (P = 0.0003 and P < 0.0001, respectively) but not with apoptosis (P = 0.1244 and P = 0.8189, respectively). Co-localization of the MT
protein and Ki-67
nuclear antigen in
breast cancer cells was demonstrated by double immunofluorescence staining. There was also significantly higher MT
protein and MT-2A
mRNA expression in histological grade 3
tumors than in histological grade 1 and 2
tumors. The finding that MT 2A appears to be the main
isoform associated with cell proliferation in invasive ductal
breast cancer tissues, may have therapeutic implications.