Metallothionein isoform 1 and 2 gene expression in the human prostate: Downregulation of MT-1X in advanced prostate cancer

Garrett, Scott H.; Sens, Mary Ann; Shukla, Deepti; Flores, L. Díaz; Somji, Seema; Todd, John H.; Sens, Donald A.

doi:10.1002/(sici)1097-0045(20000501)43:2<125::aid-pros7>3.0.co;2-s

Cited by 65 publications

(37 citation statements)

References 16 publications

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“…Although metatypic BCC is regarded as an aggressive subtype of BCC, it manifested the lowest MT-I/II expression of the analyzed subtypes. We used IHC techniques to determine MT-I/II expression, but recent studies have shown that only particular MT-I/II isoforms may contribute to cancer cell aggressiveness in some tumor types [31][32][33][34][35]. In our study, we noted the highest Ki-67 antigen expression in this subtype.…”

Section: Discussionsupporting

confidence: 78%

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Bieniek¹,

Puła²,

Piotrowska³

et al. 2012

Folia Histochem Cytobiol.

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Basal cell carcinoma (BCC) is the most frequent skin cancer, with many different histological subtypes. Recent studies have investigated the expression of proliferative markers, but little is known about the expression of metallothioneins (MT) in different histological subtypes of this cancer and their impact on proliferation intensity in BCC. In this study, we examined MT-I/II expression by immunohistochemistry in 58 different histological subtypes of BCC (38 nodular, six adenoid, eight infiltrative, and six metatypic cases) and correlated its expression with tumor size and Ki-67 proliferation rate. Statistical analysis revealed no significant differences in the expression of studied markers in regard to the histological subtype. A positive correlation between MT and Ki-67 expression was observed for all the studied cases (r = 0.26; p = 0.049), but was even stronger in the metatypic subtype of BCC (r = 0.85; p = 0.033). MT and Ki-67 expression did not correlate with tumor size. In conclusion, it seems that metallothioneins may have an impact on the proliferation rate of BCC, but further studies are required to determine whether MT may be a risk factor of recurrences.

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Section: Discussionsupporting

confidence: 78%

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Bieniek¹,

Puła²,

Piotrowska³

et al. 2012

Folia Histochem Cytobiol.

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“…The procedures for total RNA isolation, laser capture microdissection, reverse-transcription polymerase chain reaction (RT-PCR) analysis of MT-3 mRNA, and immunoblot analysis of MT-3 protein have been described previously. 8,9,11 …”

Section: Specimens For Analysis Of Mt-3 Mrna and Protein Expressionmentioning

confidence: 99%

Metallothionein Isoform 3 Overexpression Is Associated with Breast Cancers Having a Poor Prognosis

Sens¹,

Somji²,

Garrett³

et al. 2001

The American Journal of Pathology

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The third isoform (MT-3) of the metallothionein gene family is unique in that it has a limited tissue distribution, is not induced by metals, has a neuronal growth inhibitory activity, and sequesters zinc more effectively under zinc-depleted conditions. The goal of the present study was to determine whether MT-3 was absent in normal breast tissue, was overexpressed in breast cancers, and if MT-3 overexpression would be associated with disease outcome. A combination of immunohistochemistry and reverse-transcription polymerase chain reaction was used to demonstrate that the normal breast had no detectable expression of MT-3 mRNA or protein. Using immunohistochemistry, it was shown that MT-3 was overexpressed in 25 of 34 cases of breast cancer. In all cases of positive staining, MT-3 was diffusely localized to the cytoplasm. The tumors from these 34 cases were divided as to outcome based on known 5-year survival, with 20 patients being disease free at 5 years (good outcome) and the other 14 having recurring disease within 5 years (bad outcome). When analyzed for MT-3 staining, it was shown that there was a trend for increased MT-3 immunoreactivity in the group having bad outcomes. However, when the tumor subgrouping was further defined on the basis of carcinoma in situ (CIS), there was a marked significant difference in MT-3 staining between patients with good and bad outcomes. Limited to DCIS, MT-3 staining was significantly increased in patients with bad outcomes compared to those with good outcomes. Thus, these studies demonstrate that MT-3 is overexpressed in selected breast cancers and that overexpression is associated with tumors having a poor prognosis. (Am J Pathol 2001, 159:21-26) The metallothioneins (MTs) are a family of cysteine-rich, low molecular weight, intracellular proteins that bind transition metals.1 In both mice and humans, there are four classes of very similar MT proteins, designated MT-1 through -4, defined on the basis of small differences in sequence and charge characteristics.1,2 The MT-1 and MT-2 isoforms have been extensively studied, and are believed to serve an important role in the homeostasis of essential metals such as Zn 2ϩ or Cu 2ϩ during growth and development, as well as in the detoxification of heavy metals such as Cd 2ϩ and Hg 2ϩ , rendering the MTs important mediators and attenuators of heavy metal-induced toxicity, particularly hepato-and nephrotoxicity.

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“…The regulation of metallothioneins is not uniform in all tumors. For instance, this protein was overexpressed in bladder cancer but down-regulated in advanced prostate cancer (32,33). Although other metallothioneins have been found to be up-regulated by butyrate in a paradigm of increased resistance to toxic metals in tetracarcinoma and hepatoma cells (34,35), this is the first report on the regulation of metallothioneins by butyrate in colorectal cancer cells.…”

Section: Cluster B: Apoptosismentioning

confidence: 99%

Quantitative and Temporal Proteome Analysis of Butyrate-treated Colorectal Cancer Cells

Tan¹,

Tan

Lin

et al. 2008

Molecular & Cellular Proteomics

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Colorectal cancer is one of the most common cancers in developed countries, and its incidence is negatively associated with high dietary fiber intake. Butyrate, a shortchain fatty acid fermentation by-product of fiber induces cell maturation with the promotion of growth arrest, differentiation, and/or apoptosis of cancer cells. The stimulation of cell maturation by butyrate in colonic cancer cells follows a temporal progression from the early phase of growth arrest to the activation of apoptotic cascades. Previously we performed two-dimensional DIGE to identify differentially expressed proteins induced by 24-h butyrate treatment of HCT-116 colorectal cancer cells. Herein we used quantitative proteomics approaches using iTRAQ (isobaric tags for relative and absolute quantitation), a stable isotope labeling methodology that enables multiplexing of four samples, for a temporal study of HCT-116 cells treated with butyrate. In addition, cleavable ICAT, which selectively tags cysteine-containing proteins, was also used, and the results complemented those obtained from the iTRAQ strategy. Selected protein targets were validated by real time PCR and Western blotting. A model is proposed to illustrate our findings from this temporal analysis of the butyrateresponsive proteome that uncovered several integrated cellular processes and pathways involved in growth arrest, apoptosis, and metastasis. These signature clusters of butyrate-regulated pathways are potential targets for novel chemopreventive and therapeutic drugs for treatment of colorectal cancer. Molecular & Cellular Proteomics 7:1174 -1185, 2008.In developed countries, colorectal cancer is a prevalent disease with high mortality and morbidity rates (1). This disease has emerged as the top malignancy in Singapore. Environmental factors are responsible for about 80% of the cases, whereas genetic predisposition accounts for the minority 20% of cases. Epidemiological evidence suggests that high intake of dietary fiber reduces the incidence and risk of this neoplasm (2, 3). A wealth of studies has shown that butyrate produced from anaerobic fermentation of indigestible carbohydrate is the molecule responsible for the chemopreventive properties of a fiber-rich diet (4 -6).Although butyrate serves as an energy source for normal colonocytes, in vivo and in vitro studies have shown that at physiological concentrations this natural short-chain fatty acid mediates cell maturation with the promotion of growth arrest followed by differentiation and/or apoptosis of cancer cells (7-11). These biological effects are crucial in colorectal cancer therapy as colonic transformation is characterized by multistage alterations of tissue homeostasis resulting in aberrant cell division and/or cell death (12, 13). Butyrate has been purported as a potential anticancer agent. This initiated notable research in identifying proteins that contribute to its biological effects (14, 15). However, most of these investigations focused on one target at any one time and were thus unable to systematica...

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Metallothionein isoform 1 and 2 gene expression in the human prostate: Downregulation of MT-1X in advanced prostate cancer

Cited by 65 publications

References 16 publications

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Metallothionein Isoform 3 Overexpression Is Associated with Breast Cancers Having a Poor Prognosis

Quantitative and Temporal Proteome Analysis of Butyrate-treated Colorectal Cancer Cells

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