Estrogen Response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the coexistence of multiple estrogen-deprivation resistant mechanisms

Fujiki, N. M.; Konno, Hirotaka; Kaneko, Yosuke; Gohno, Tatsuyuki; Hanamura, Toru; Imami, Koshi; Ishihama, Yasushi; Nakanishi, Kyoko; Niwa, Toshimitsu; Seino, Yutaka; Yamaguchi, Yuri; Hayashi, Shin Ichi

doi:10.1016/j.jsbmb.2013.08.012

Cited by 22 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of the present study demonstrated that an increase binding with FEN1 and ERα occurred concomitantly with an increase in FEN1 expression, suggesting a correlation between FEN1 and ERα in trastuzumab sensitivity. It has been reported that pS2, PgR and EGR3 are able to be transcribed by ERα (20). The present findings also showed that the mRNA levels of ERα target genes were increased in trastuzumab-treated cells and were partially restored by knockdown of FEN1.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells

Zeng

Che

Liu

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0.05). It was also revealed that trastuzumab induced HER receptor activation, increased binding with FEN1 and estrogen receptor α (ERα), and upregulated ERα-target gene transcription (P<0.05). Upon silencing of FEN1 expression with siRNA, activation of HER receptor and FEN1 binding to ERα were decreased, and trastuzumab-induced ERα target gene upregulation was partially ameliorated (P<0.05). These results suggest that FEN1 may mediate trastuzumab resistance via inducing HER receptor activation and enhancing ERα-target gene transcription. The findings of the present study indicate a novel role of FEN1 in trastuzumab resistance, suggesting that targeting FEN1 may enhance the efficiency of trastuzumab as a treatment for HER2-positive breast cancer.

show abstract

Section: Discussionsupporting

confidence: 80%

“…4A). Relative mRNA expression levels of ERα target genes were investigated using RT-qPCR (20) and the levels of pS2, PgR and EGR3 were increased in trastuzumab-treated cells by 6.78-, 3.54-and 2.2-fold compared with NC cells, respectively (all P<0.05; Fig. 4B).…”

Section: Trastuzumab Increases Binding Of Fen1 With Erα and Fen1 Knocmentioning

confidence: 99%

FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells

Zeng

Che

Liu

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…We have established several AI-resistant cell lines that depend on an ER-mediated pathway from MCF-7 cells [36,37]. Moreover, there have been many reports that the LTED (long-term estradiol deprivation) cells overexpressed ER [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Androgen metabolite-dependent and estrogen-depletion-resistant cells derived from the MCF-7 cells were recently reported to show dose-dependent activation of ER functions by the estrogenic androgen 5a-androstane-3b,17b-diol (3b-diol) and markedly decreased AR expression [36]. In addition, several ER-independent proliferative pathways have been reported as AI-resistance mechanisms, including up-regulation of the ER-mediated pathway [5,6], the growth factor receptor-mediated pathways [7,8], mitogen-activated protein kinase (MAPK), and phosphatidylinositide 3-kinase (PI3K)/Akt [6,9,37]. Therefore, acquired AI-resistance mechanisms are suggested to be diverse and appropriately targeted therapies, according to case are required.…”

Section: Discussionmentioning

confidence: 99%

Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma

Fujii

Hanamura

Suzuki

et al. 2014

The Journal of Steroid Biochemistry and Molecular Biology

Self Cite

View full text Add to dashboard Cite

“…This is particularly true in ER-dependent MCF-7 cells under a long-term estrogen-depletion culture. In these cells, the ER gets hyper-phosphorylated through the Akt pathway, compensating for estrogen depletion and resulting in enhanced expression of ER-target genes [42]. PCP4/PEP19 was constitutively and highly expressed in ER-negative SK-BR-3 cells, mimicking the ER-signal independent condition with a compensatory expression of anti-apoptotic PCP4/PEP19 for cell survival.…”

Section: Discussionmentioning

confidence: 99%

Anti-apoptotic Effects of PCP4/PEP19 in Human Breast Cancer Cell Lines: A Novel Oncotarget

et al. 2014

View full text Add to dashboard Cite

The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-AktThr308, enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-AktThr308 and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.

show abstract

Estrogen Response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the coexistence of multiple estrogen-deprivation resistant mechanisms

Cited by 22 publications

References 35 publications

FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells

FEN1 knockdown improves trastuzumab sensitivity in human epidermal growth factor 2-positive breast cancer cells

Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma

Anti-apoptotic Effects of PCP4/PEP19 in Human Breast Cancer Cell Lines: A Novel Oncotarget

Contact Info

Product

Resources

About