Targeting Metallothionein for Prognosis and Treatment of Breast Cancer

Lai, Yiyang; Yip, George; Bay, Boon‐Huat

doi:10.2174/157489211795328495

Cited by 13 publications

(10 citation statements)

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“…Although the key roles of MTs in mediating heavy metal detoxification have been abundantly documented (20), their implication in the control of gene transcription is still unclear. It has been proposed that MT could bind to the p50 subunit of the NF-κB complex, thereby increasing its ability to act as a transcriptional activator (21).…”

Section: Discussionmentioning

confidence: 99%

Metallothioneins negatively regulate IL-27–induced type 1 regulatory T-cell differentiation

Pot

Apétoh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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IL-27–induced type 1 regulatory T (Tr1) cells suppress autoimmunity by producing IL-10. Signal transducer and activator of transcription (STAT) 1 and STAT3 have been described as key transcription factors that promote IL-10 secretion from Tr1 cells induced by IL-27. However, the molecular pathways for negatively regulating Tr1 cell differentiation remain elusive. Here, we show that IL-27 induces metallothioneins (MTs) that in turn prevent Tr1 cell development. MT expression leads to the reduction of STAT1 and STAT3 phosphorylation under Tr1 differentiation condition, resulting in impaired IL-10 production. Accordingly, Tr1 cells derived from MT-deficient mice showed an increased ability to produce IL-10 and potently suppress experimental autoimmune encephalomyelitis upon adoptive transfer. Moreover, activation of STAT1 and/or STAT3 can overcome the suppression of IL-10 by MTs, indicating a dynamic balance between STATs and MTs in regulating IL-10 during Tr1 cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Metallothioneins negatively regulate IL-27–induced type 1 regulatory T-cell differentiation

Pot

Apétoh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…MTs, because of their roles in tumors, can be targeted for cancer therapy (Lai et al, 2011). Silencing of MT by short interfering RNA (siRNA) was published by Tarapore et al, who used phage Phi29 motor pRNA as a vehicle to carry siRNA specifically targeted to MT-2A mRNA in ovarian cancers (Tarapore et al, 2011), and by Lai et al, who reported that silencing of the MT-2A gene by siRNA induces entosis (a process involving the invasion of one cell into another, and internalized cells are either degraded by lysosomal enzymes or released) in adherent MCF-7 breast cancer cells (Lai et al, 2010).…”

Section: Mts In Cancer Therapymentioning

confidence: 99%

Metallothioneins and zinc in cancer diagnosis and therapy

Křížková¹,

Ryvolová²,

Hraběta³

et al. 2012

Drug Metabolism Reviews

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Metallothioneins (MTs) are involved in protection against oxidative stress (OS) and toxic metals and they participate in zinc metabolism and its homeostasis. Disturbing of zinc homeostasis can lead to formation of reactive oxygen species, which can result in OS causing alterations in immunity, aging, and civilization diseases, but also in cancer development. It is not surprising that altered zinc metabolism and expression of MTs are of great interest in the case of studying of oncogenesis and cancer prognosis. The role of MTs and zinc in cancer development is tightly connected, and the structure and function of MTs are strongly dependent on Zn²⁺ redox state and its binding to proteins. Antiapoptic effects of MTs and their interactions with proteins nuclear factor kappa B, protein kinase C, esophageal cancer-related gene, and p53 as well as the role of MTs in their proliferation, immunomodulation, enzyme activation, and interaction with nitric oxide are reviewed. Utilization of MTs in cancer diagnosis and therapy is summarized and their importance for chemoresistance is also mentioned.

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“…This may be the pathological basis of breast cancer [21]. In this study, RT-PCR and western blot methods were used to detect the expressions of the autophagy-related gene, Beclin1, as well as apoptosisrelated genes Bcl-2 and Bax in breast cancer tissues.…”

mentioning

confidence: 99%

The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax in breast cancer tissues

Yao

Chen

et al. 2011

Tumor Biol.

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The purpose of this study was to detect the expression of autophagy-related gene Beclin1 and apoptosis-related genes Bcl-2 and Bax in breast cancer tissues, to investigate their relationship and significance to the occurrence and development of breast cancer, and to provide an experimental basis for the biological treatment of breast cancer in the future. Human breast cancer tissues and relatively healthy breast tissue adjacent to the tumor were collected during surgical resection. By using RT-PCR and western blot, the mRNA and protein expressions of Beclin1, Bcl-2, and Bax were detected in the breast cancer tissues and the relatively healthy, adjacent tissues. The correlations of these expressions with the occurrence, development, and clinicopathology of breast cancer were analyzed. The mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues were significantly lower than those in the relatively healthy, adjacent breast tissues (p < 0.05); the lower the degree of tumor differentiation, the lower the mRNA and protein expressions of Beclin1 and Bcl-2 (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for lymph node metastasis were significantly lower than those negative for lymph node metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for distant metastasis were significantly lower than those negative for distant metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for ki67 were significantly lower than those negative for ki67 (p < 0.05). The mRNA and protein expressions of Bax were different from those of Beclin1 and Bcl-2. In breast cancer tissues, the mRNA and protein expressions of Bax were up-regulated (p < 0.05); the lower the degree of tumor differentiation, the higher the mRNA and protein expressions of Bax (p < 0.05); the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for lymph node metastasis were significantly higher than those negative for lymph node metastasis (p < 0.05); and the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for distant metastasis were significantly higher than those in patients negative for distant metastasis (p < 0.05). However, the mRNA and protein expressions of these three genes were not correlated with patient age, tumor size, progesterone receptor positivity, or human epidermal growth factor positivity (p > 0.05). The correlation of Bcl-2 and Bax mRNA with Beclin1 mRNA expressed in breast cancer tissues were both statistically significant (p < 0.05). The activity change of autophagy and apoptosis is associated with the tumorigenesis and tumor progression of breast cancer. The joint detection of these three genes (Beclin1, Bcl-2, and Bax) contributes to the early diagnosis of and predicts prognosis for breast cancer, and this also provides an experimental basis for the biological th...

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Targeting Metallothionein for Prognosis and Treatment of Breast Cancer

Cited by 13 publications

References 0 publications

Metallothioneins negatively regulate IL-27–induced type 1 regulatory T-cell differentiation

Metallothioneins negatively regulate IL-27–induced type 1 regulatory T-cell differentiation

Metallothioneins and zinc in cancer diagnosis and therapy

The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax in breast cancer tissues

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