title: Metallothionein 2A expression is associated with cell proliferation in breast cancer.
abstract: 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.
authors.affiliation: Anatomy Department, National University of Singapore, 4 Medical Drive, S117 597 Singapore.
authors.forename: Rongxian
authors.initials: R
authors.lastname: Jin
authors.forename: Vincent T-K
authors.initials: VT
authors.lastname: Chow
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: S Thameem
authors.initials: ST
authors.lastname: Dheen
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D008668:Metallothionein