GPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells

The IGF-I receptor (IGF-IR) has an important role in breast cancer development and progression. Previous studies have suggested that the IGF-IR gene is negatively regulated by a number of transcription factors with tumor suppressor activity, including the Wilms’ tumor protein WT1. The present study was aimed at evaluating the hypothesis that IGF-IR gene transcription in breast cancer cells is under inhibitory control by WT1 and, furthermore, that the mechanism of action of WT1 involves functional and physical interactions with estrogen receptor-α (ERα). Results of transient coexpression experiments showed that all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9) repressed IGF-IR promoter activity by 39–49%. To examine the potential interplay between WT1 and ERα in control of IGF-IR gene transcription we employed ER-depleted C4 cells that were generated by clonal selection of ER-positive MCF-7 cells that were maintained in estrogen-free conditions. IGF-IR levels in C4 cells were ~43% of the values in MCF-7 cells whereas WT1 levels in C4 cells were 4.25-fold higher than in MCF-7. Triple cotransfection experiments using an ERα expression vector in the absence or presence of WT1 expression vectors, along with an IGF-IR promoter reporter plasmid, revealed that ERα stimulated IGF-IR promoter activity whereas coexpression of WT1 abrogated the effect of ERα. In addition, co-immunoprecipitation experiments demonstrated a specific association between WT1 and ERα. Combined, our results suggest that WT1 suppresses IGF-IR gene transcription in breast cancer cells via a mechanism that involves protein–protein association with ERα. As a result of this interaction, the ability of ERα to transactivate the IGF-IR promoter is abrogated. These findings are consistent with a potential tumor suppressor role for WT1 in breast cancer and suggest that WT1 inactivation in tumoral cells may result in deregulated IGF-IR gene expression and enhanced mitogenic activation by locally produced and/or circulating IGFs.

Download Full-text

Ethanol Extract of Cordia myxa L Fruit Increase Expression of Antioxidant Enzymes and Tumor Suppressor PTEN Genes in MCF-7 Breast Cancer Cells

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2021.13.02.006 ◽

2021 ◽

Vol 13 (02) ◽

Keyword(s):

Breast Cancer ◽

Antioxidant Enzymes ◽

Tumor Suppressor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Ethanol Extract ◽

Cordia Myxa ◽

Mcf 7

Download Full-text

Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via Integrating ERK/JNK Pathway

10.21203/rs.3.rs-58828/v1 ◽

2020 ◽

Author(s):

Jianghong Cheng ◽

Mingli Li ◽

Chi-Meng Tzeng ◽

Xingchun Gou ◽

Shuai Chen

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Suppressor ◽

Cell Viability ◽

Cancer Cells ◽

Invasive Breast Cancer ◽

Breast Cancer Cells ◽

Suppressor Gene ◽

Pathological Stages ◽

Mcf 7

Abstract Background: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, there is no report of ST5 expression or function in the progression of breast cancer.Methods: ST5 expression in different subtypes and pathological stages of breast cancer was determined by Oncomine database, Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4) analysis and immunohistochemistry. Cell viability was measured by CCK8 assay and metastatic behavior was assessed using scratch wound model and Transwell. Flow cytometry was employed for cell cycle and apoptosis detection, and methylation-specific PCR (MSP) was used to detect methylation level.Results: ST5 was expressed at low level in different subtypes of breast cancer specimens compared to normal breast and there was a negative association between ST5 status and pathological stages of breast cancer patients. Additionally, ST5 was lower in cases of recurrent and invasive breast cancer than that in non-recurrent and non-invasive patients. In in vitro experiment, ST5 status was also negatively associated with the invasive capability of breast cancer cells, showing lower in MDA-MB-231 and SKBR3 cell lines than that in MCF-7 cells. ST5-downregulation promoted, while ST5-upregulation inhibited the tumour characteristics of MDA-MB-231 cells including cell viability, cell cycle and migration. And exogenous ST5 also elevated, but ST5 depletion limited the proportion of apoptotic cells in MDA-MB-231 cells. However, the alteration of ST5, no matter upregulation or downregulation, had no impact on tumour behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated JNK and ERK1/2, and subsequently the expression of c-Myc. Of note, low level of ST5 in breast cancer cells was possibly related with the aberrant methylation of ST5 promoter region.Conclusion: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

Download Full-text

Effect of the tumor suppressor gene ING4 on the proliferation of MCF-7 human breast cancer cells

Oncology Letters ◽

10.3892/ol.2012.744 ◽

2012 ◽

Vol 4 (3) ◽

pp. 438-442 ◽

Cited By ~ 14

Author(s):

QINJUN WEI ◽

WEI HE ◽

YAJIE LU ◽

JUN YAO ◽

XIN CAO

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Tumor Suppressor Gene ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Suppressor Gene ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

Download Full-text

Apoptotic effect of Physalis minima Linn ethanol extract on breast cancer cells via p53 wild-type and Apaf-1 protein

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i10.10 ◽

2020 ◽

Vol 19 (10) ◽

pp. 2085-2089

Author(s):

Handayani Handayani ◽

Retno Handajani ◽

Imam Susilo ◽

Achmad Basori ◽

Hotimah Masdan Salim

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Cell Line ◽

Breast Cancer Cells ◽

Ethanol Extract ◽

Tumor Suppressor Protein ◽

Tumor Suppressor Protein P53 ◽

Protein P53 ◽

Mcf 7

Purpose: To produce an anti-cancer agent from Physalis minima ethanol extract as well as prevent the growth of NMU-induced breast cancer and MCF-7 cell line.Methods: This research used an animal model (Wistar-Furth rats), and cell line used in this study was normal breast-cell line MCF-7. The rats were administered with the ethanol extract of Physalis minima Linn (100, 250 and 400 mg/kg/day) by gavage, once a day for 4 weeks. Meanwhile, MCF-7 cell lines were cultured in medium and incubated in 100 μg/mL of ethanol extract of Physalis minima for 48 h. The samples were analyzed using histology and immunohistochemistry techniques for expression of p53 antibody DO-1 and APAF-1.Results: The results of immunohistological analysis in the breast organ showed that Physalis minima Linn extract significantly (p < 0.05) increased the tumor suppressor protein p53 at doses of 100, 250 and 400 mg/kg/day. In addition, the extract also significantly (p < 0.05) increased APAF-1, which is a gene determining cell death, at doses of 100, 200 and 400 mg/day.Conclusion: Ethanol extract of Physalis minima Linn inhibits the cytotoxic activity of NMU-induced breast cancer by increasing the tumor suppressor protein p53 and APAF-1. Thus, Physalis minima Linn extract can potentially be used as a complementary treatment for inhibiting the growth of breast cancer cells in patients. Keywords: Apoptosis protease-activating factor-1, Breast cancer, MCF-7 cell line, Physalis minima, p53

Download Full-text

Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.621500 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianghong Cheng ◽

Mingli Li ◽

Chi-Meng Tzeng ◽

Xingchun Gou ◽

Shuai Chen

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Tumor Suppressor Gene ◽

Invasive Breast Cancer ◽

Breast Cancer Cells ◽

Suppressor Gene ◽

And Migration ◽

Invasive Capability ◽

Mcf 7

BackgroundSuppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague.MethodsOnline database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation.ResultsLow level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region.ConclusionOur findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

Download Full-text