Identification of differentially expressed genes in human breast cancer cells induced by 4-hydroxyltamoxifen and elucidation of their pathophysiological relevance and mechanisms

Fang, Qi; Yao, Shuang; Luo, Guanghua; Zhang, Xiaoying

doi:10.18632/oncotarget.23504

Cited by 25 publications

(21 citation statements)

References 86 publications

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“…It has been reported that an increase of TG2 expression confers a growth advantage to cancer cells, enabling them to survive in hypoxic conditions. TG2 overexpression seems to be associated with the proliferation and metastasis of various tumours, such as breast cancer, ovarian cancer, lung cancer and colorectal carcinoma [32][33][34][35][36]. Several reports proposed TG2 inhibition as a useful tool for therapeutic approaches.…”

Section: Resultsmentioning

confidence: 99%

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Currò

Ferlazzo

Giunta

et al. 2020

IJMS

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Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.

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Section: Resultsmentioning

confidence: 99%

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Currò

Ferlazzo

Giunta

et al. 2020

IJMS

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“…On the other hand, the signi cance in cluster E is rather di cult to interpret. Some groups have previously reported that interferon regulatory factor-1 (IRF1) is critical for TAM-mediated apoptosis, and its related pathway is also up-regulated in TAM-treated cells 28 . IRF1 was shown to induce apoptosis in breast cancer cells 29 .…”

Section: Discussionmentioning

confidence: 99%

Mathematical Modeling and Transcriptome Profiling of Breast Cancer Cells During Tamoxifen Treatment Reveal Multiple Trajectories for Resistant Subtypes

Magi

Ki²,

Ukai³

et al. 2021

Preprint

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Cancer cells acquire drug resistance through following non-resistant, pre-resitant and resistant stages. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here, we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing of tamoxifen-treated cells revealed that tamoxifen-resistant cells can be subgrouped into two, one showing cancer stem cell-like metabolic regulation and the other showing high expression of genes encoding adhesion molecules and histone modifying-enzymes. Pseudotime analyses showed a cell transition trajectory to the two resistant subgroups that stems from shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted that inhibition of transition to both subtype would be required to prevent the appearance of tamoxifen resistance.

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“…Numerous studies have demonstrated that TGM2 expression is closely associated with the proliferation and metastasis of various malignant tumor cells (40–43). TGM2 expression is increased in breast cancer, ovarian cancer, lung cancer and CRC (44–47). Similar to previous findings (45), the present data also demonstrated that TGM2 expression was increased in CRC tissues.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑214 suppresses the viability, migration and invasion of human colorectal carcinoma cells via targeting transglutaminase 2

2019

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Colorectal carcinoma (CRC) is a common malignancy of the digestive tract. MicroRNA (miR)-214 is considered a key hub that controls tumor networks; therefore, the effects of miR-214 on CRC were examined and its target gene was investigated in this study. The expression levels of transglutaminase 2 (TGM2) and miR-214 were detected in CRC and adjacent normal tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, and luciferase activity was analyzed by dual luciferase reporter analysis. In addition, cell viability, invasion and migration were measured by Cell Counting kit-8 and Transwell assays, respectively. The expression levels of epithelial-mesenchymal transition-related proteins, and phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) signaling-associated factors were detected using RT-qPCR and western blotting. The results demonstrated that miR-214 expression was downregulated in CRC tissue, whereas TGM2 expression was upregulated. According to TargetScan prediction, miR-214 possesses a binding site to TGM2. In addition, transfection with miR-214 mimics markedly suppressed the viability of LoVo cells. miR-214 overexpression also inhibited cell invasion and migration by increasing E-cadherin and tissue inhibitor of metalloproteinases-2 expression, and decreasing matrix metalloproteinase (MMP)-2 and MMP-9 expression. Furthermore, miR-214 downregulated phosphorylation of PI3K and Akt; however, the expression levels of total PI3K and Akt were not affected by miR-214. In conclusion, this study indicated that TGM2 was a target gene of miR-214, and a negative correlation between miR-214 and TGM2 expression was determined in CRC. Notably, miR-214 markedly suppressed the viability, invasion and migration of CRC cells, which may be associated with a downregulation in PI3K/Akt signaling. These findings suggested that miR-214 may be considered a novel target for the treatment of CRC.

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Identification of differentially expressed genes in human breast cancer cells induced by 4-hydroxyltamoxifen and elucidation of their pathophysiological relevance and mechanisms

Cited by 25 publications

References 86 publications

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Mathematical Modeling and Transcriptome Profiling of Breast Cancer Cells During Tamoxifen Treatment Reveal Multiple Trajectories for Resistant Subtypes

MicroRNA‑214 suppresses the viability, migration and invasion of human colorectal carcinoma cells via targeting transglutaminase 2

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