Metallothionein as a Prognostic Biomarker in Breast Cancer

Bay, Boon‐Huat; Jin, Rong; Huang, Jingxiang; Tan, Puay‐Hoon

doi:10.1177/153537020623100910

Cited by 44 publications

(41 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar pattern of MT expression was observed in the examined benign lesions of mammary gland, including adenomas, adenofibromas and papillomas [37]. In lobular breast cancers as well as in other, less frequent histological types of the tumour, including mucinous carcinoma and papillary carcinoma, in most cases no MT expression or weak cytoplasmic reactions was shown [13,15]. On the other hand, a definitely increased MT expression was noted in ductal breast cancer, both in in situ and invasive forms.…”

Section: Discussionsupporting

confidence: 74%

“…It is suggested that the role of MT in carcinogenesis and tumour progression could be linked to the involvement of MT in processes of cell proliferation and differentiation [10,12,13]. Using flow cytometry, the highest concentration of MT was found in cells at the end of G1 phase and at the threshold of G1/S phases [38].…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested that role of the proteins in carcinogenesis is linked to their involvement in processes of cells proliferation and differentiation [12,13]. There have been proposed various mechanisms of MT influence on proliferation of cells and progression of tumours.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers.

Gomułkiewicz

Podhorska-Okołów²,

Szulc³

et al. 2010

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:Our study aimed at examining significance of metallothionein (MT) expression in ductal breast cancers by determination of a relationship between expression of MT protein (MT-1/2) and selected prognostic factors, including grade of histological differentiation (G), expression of Ki-67 proliferative antigen, expression of estrogen receptors (ER) and progesterone receptors (PgR) and expression of HER-2 receptor. Material for the studies involved 54 samples of invasive ductal breast cancer, manifesting malignancy grades of G1-G3. In paraffin sections of examined tumours immunohistochemical reactions were performed using specific antibodies directed to MT, Ki-67, ER, PgR or HER-2. Intensity of MT-specific immunohistochemical reactions was measured using the semiquantitative IRS scale of Remmele. Intensity of colour reactions targeted at Ki-67, ER, PgR was evaluated scoring proportions of positive cells, while HER-2-specific reactions were evaluated in the scale of 0-3 points. The lowest level of MT expression was detected in breast cancer cases of G1 malignancy grade (G1 vs G3 p=0.020). A positive correlation between MT and Ki-67 antigen expression (r=0.32, p=0.019) was disclosed. Moreover, MT expression exhibited negative correlations with expression of ER (r=-0.35, p=0.008) and PgR (r=-0.27, p=0.046). No relationships could be detected between expression of MT and expression of HER-2 (r=0.12, p=0.37). The obtained results suggest that MT expression might be helpful in prognostic evaluation of ductal breast cancers. Abbreviations: MT -metallothionein; Ki-67 -proliferative antigen; ER -estrogen receptor; PgR -progesterone receptor; HER-2 -human epidermal growth factor receptor 2; G -grade of histological differentiation; IRS -immuno-reactive score

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers.

Gomułkiewicz

Podhorska-Okołów²,

Szulc³

et al. 2010

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, leptin stimulated a 40-fold induction in metallothionein 3 (MT3) gene expression. Metallothioneins are low-molecular-weight metal-binding proteins associated with proliferation, are overexpressed during breast cancer, and serve as potential biomarkers for poor cancer prognosis (Sens et al 2001, Bay et al 2006.…”

Section: Leptin Regulates Expression Of Cell Cycle and Apoptosis Genesmentioning

confidence: 99%

Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

Perera¹,

Chin²,

Duru³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

Obesity is a recently established risk factor for breast cancer incidence and mortality. A characteristic of obesity is elevated circulating levels of adipocyte-derived hormone leptin. Evidence indicates that leptin plays an important role in mammary tumor formation; however, the mechanisms involved are poorly understood. Toward better defining the role of leptin in breast cancer, we describe the identification of leptin-regulated genes in hormone-responsive Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells using a microarray system. More than 64 leptin-regulated genes were identified including those for growth factors, cell cycle regulators, extracellular matrix (ECM) proteins, and genes associated with metastasis. Cell cycle genes up-regulated by leptin include cyclins D and G, cyclin-dependent kinase 2, p21, p27, and p16. Leptin suppressed the expression of transforming growth factor-b , a cell cycle suppressor. Determining the significance of this effect, treatment of MCF-7 cells with TGFB1 abrogated leptin-stimulated proliferation. Leptin up-regulated the expression of connective tissue growth factor, villin 2, and basigin, factors that are associated with ECM and are known to impact tumor growth. Finally, leptin induced the expression of anti-apoptotic genes BCL2 and survivin, and reduced the expression of apoptotic genes. The effect of leptin on MCF-7 survival was evaluated via TUNEL assay and demonstrated a sixfold reduction in apoptosis in leptin-treated cells, compared with controls. These data suggest leptin promotes mammary tumor growth through multiple mechanisms, including regulating the cell cycle, apoptosis, and by modulating the extracellular environment. The identification of leptinregulated genes begins to provide mechanistic links into the relationship between obesity and breast cancer incidence and morbidity.

show abstract

“…It is therefore not surprising that aberrant expression patterns of MTs can correlate with a number of pathologic conditions, including malignant progression. For example, high levels of MT-I and MT-IIA have been detected in many (but not all) human tumors, including those of the breast, prostate, cervix, testes, kidney, bladder, brain, and oral epithelium (19)(20)(21)(22)(23)(24)(25). Underlying molecular mechanisms are believed to include the ability of MT to activate survival pathways and confer resistance against drug and radiation therapy (5,(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Metallothionein Induction by Hypoxia Involves Cooperative Interactions between Metal-Responsive Transcription Factor-1 and Hypoxia-Inducible Transcription Factor-1α

Murphy

Kimura

Sato

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

Mammalian metallothionein (MT) genes are transcriptionally activated by the essential metal zinc as well as by environmental stresses, including toxic metal overload and redox fluctuations. In addition to playing a key role in zinc homeostasis, MT proteins can protect against metal-and oxidant-induced cellular damage, and may participate in other fundamental physiologic and pathologic processes such as cell survival, proliferation, and neoplasia. Previously, our group reported a requirement for metal-responsive transcription factor-1 (MTF-1) in hypoxia-induced transcription of mouse MT-I and human MT-IIA genes. Here, we provide evidence that the protumorigenic hypoxia-inducible transcription factor-1A (HIF-1A) is essential for induction of MT-1 by hypoxia, but not zinc. Chromatin immunoprecipitation assays revealed that MTF-1 and HIF-1A are both recruited to the mouse MT-I promoter in response to hypoxia, but not zinc. In the absence of HIF-1A, MTF-1 is recruited to the MT-I promoter but fails to activate MT-I gene expression in response to hypoxia. Thus, HIF-1A seems to function as a coactivator of MT-I gene transcription by interacting with MTF-1 during hypoxia. Coimmunoprecipitation studies suggest interaction between MTF-1 and HIF-1A, either directly or as mediated by other factors. It is proposed that association of these important transcription factors in a multiprotein complex represents a common strategy to control unique sets of hypoxia-inducible genes in both normal and diseased tissue. (Mol Cancer Res 2008;6(3):483 -90)

show abstract

Metallothionein as a Prognostic Biomarker in Breast Cancer

Cited by 44 publications

References 59 publications

Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers.

Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers.

Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

Metallothionein Induction by Hypoxia Involves Cooperative Interactions between Metal-Responsive Transcription Factor-1 and Hypoxia-Inducible Transcription Factor-1α

Contact Info

Product

Resources

About