Significance of metallothionein expression in breast myoepithelial cells

Abstract

Metallothioneins (MTs), a group of cysteine-rich proteins with a small molecular mass, are known to have metalloregulatory functions. MT gene expression has been demonstrated to be cell type-specific and differentially regulated (possibly related to their germ layer origin and different functional states). In vitro studies suggest that MT-2A, MT-IE, and MT-1F isoforms may be related to breast cancer. In this study, data on MT-2A, MT-1E, MT-1F mRNA analysis via reverse transcription-polymerase chain reaction in invasive ductal breast cancer tissues and their adjacent benign breast tissues from 27 mastectomies are presented. Expression of mRNA in all the three MT isoforms was detected in both cancerous and adjacent benign breast tissues (with MT-2A mRNA expression being the highest). MT-1F expression was significantly higher in benign breast tissues compared with the breast cancers (P=0.017). In situ hybridization confirmed the expression of MT-2A mRNA in the myoepithelial cells of the breast tissues. Immunohistochemical localization of the MT protein revealed that myoepithelial cells consistently expressed the MT protein, while the cancer cells expressed MT with great variation. Based on our immunohistochemical and mRNA analysis, it is likely that the three MT isoforms are specifically expressed in myoepithelial cells of benign breast tissues and cancer cells of the invasive ductal breast cancer tissues. As MT expression occurs in myoepithelial cells and ductal breast cancer cells, our finding supports the proposition that loss of myoepithelial cells in invasive mammary cancers may be compensated in part by changes in the tumor cells, which may subsequently be the basis for studying the role of MT in breast physiology and carcinogenesis. Differential MT-1F expression in breast myoepithelial cells warrants further study.

eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer

“…MT2A gene belongs to the metallothionein families, which are important for metal ion homeostasis. It was reported to be associated with breast cancer (Jin et al, 2002) and tumor grade (Jin et al, 2004) and is related to the chemoresistance of ovarian cancer (L' Espe´rance et al, 2006). The protein level of these genes affected by silencing eIF3m and their mRNA level also changed in a similar pattern (Figure 7).…”

Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

“…5 Strong expression of metallothionein is seen in simple epithelia, basal, and myoepithelial cells, specially in normal and neoplastic breast tissue. 6 Increased expression of the MT genes is also noted in tumors of the colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testis, thyroid, and urinary bladder. 7,8 Maspin is a mammary serine protease inhibitor with homology to members of the serpin family of protease inhibitors.…”

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

“…17) The most abundant isoform, MT2A, was reported to regulate cell proliferation and apoptosis. 18) More recently, silencing of the MT2A gene inhibited cell cycle progression in breast cancer cells. 19) MT2A mRNA expression was reduced in NHBE and DHBE (COPD) cells by SWCNT exposure.…”