Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

Moerkens, Marja; Zhang, Y.; Wester, Lynn; Water, Bob van de; Meerman, John H.N.

doi:10.1186/1471-2407-14-283

Cited by 70 publications

(50 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To develop breast cancer therapies, targeting of ERa, which is highly expressed in approximately 70% of all breast tumors (21), is taken as a targeting molecule.…”

Section: Discussionmentioning

confidence: 99%

ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells

Zheng

Zhang

Huang

et al. 2015

Journal of Pharmacological Sciences

View full text Add to dashboard Cite

The estrogen receptor alpha (ERα) has been proven to be one of the most important therapeutic targets in breast cancer over the last 30 years. Previous studies pointed out that a natural flavonoid, silibinin, induced apoptosis in human breast cancer MCF-7 cells. In the present study we report that exposure of MCF-7 cells to silibinin led to cell death through the down-regulation of ERα expression. Silibinin-induced apoptosis of MCF-7 cells through up-regulation of caspase 6 due to ERα signalling repression was further boosted by ERα antagonist. Moreover, up-regulation of autophagy induced by silibinin accounted for apoptotic exacerbation, being further enhanced by ERα inhibition. Upon ERα activation, series of downstream signalling pathways can be activated. We found that silibinin reduced the expressions of Akt/mTOR and extracellular-signal-related kinase (ERK), which respectively accounted for the induction of autophagy and apoptosis. These effects were further augmented by co-treatment with ERα inhibitor. We conclude that the treatment with silibinin of ERα-positive MCF-7 cells down-regulates the expression of ERα, and subsequently mTOR and ERK signaling pathways, ERα downstream, finally resulting in induction of autophagy and apoptosis.

show abstract

“…To develop breast cancer therapies, targeting of ERa, which is highly expressed in approximately 70% of all breast tumors (21), is taken as a targeting molecule.…”

Section: Discussionmentioning

confidence: 99%

ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells

Zheng

Zhang

Huang

et al. 2015

Journal of Pharmacological Sciences

View full text Add to dashboard Cite

show abstract

“…Compensatory relationships exist between ER and growth factor signaling, where blockage of one of them may lead to activation of the other [12,13,[16][17][18]51], and it has recently been shown that EGF-driven signaling can overrule tamoxifenmediated inhibition of MCF-7 breast cancer cell proliferation [52]. Thus, combinatorial treatment blocking both ER and growth factor signaling pathways has been suggested to be the most effective inhibition of proliferation in ER positive breast cancer cells [12,16,51,53,54].…”

Section: Treatment With Ais For 3-4 Months Suppresses Total Body Estrmentioning

confidence: 99%

Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive/HER-2/neu non-amplified primary breast cancers

Flågeng

Larionov

Geisler

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

While estrogens have been shown to modulate EGFR/HER-1 and HER-2/neu expression in experimental systems, the effects of estrogen deprivation on expression levels of the HER-receptors and the neuregulin (NRG)1 ligand in breast cancers remain unknown. Here, we measured EGFR/HER-1-4 and NRG1 mRNA in ER positive tumors from 85 postmenopausal breast cancer patients before and after two weeks (n=64) and three months (n=85) of primary treatment with an aromatase inhibitor (AI). In tumors lacking HER-2/neu amplification, quantitative real-time PCR analyses revealed EGFR/HER-1 and NRG1 to vary significantly between the three time points (before therapy, after 2 weeks and after 3 months on treatment; P≤0.001 for both). Pair-wise comparison revealed a significant increase in EGFR/HER-1 already during the first two weeks of treatment (P=0.049) with a further increase for both EGFR/HER-1 and NRG1 after 3 months on treatment (P≤0.001 and P=0.001 for both comparing values at 3 months to values at baseline and 2 weeks respectively). No difference between tumors responding versus non-responders was recorded. Further, no significant change in any parameter was observed among HER-2/neu amplified tumors. Analyzing components of the HER-2/neu PI3K/Akt downstream pathway, the PIK3CA H1047R mutation was associated with treatment response (P=0.035); however no association between either AKT phosphorylation status or PIK3CA gene mutations and EGFR/HER-1 or NRG1 expression levels were observed. Our results indicate primary AI treatment to modulate expression of HER-family members and the growth factor NRG1 in HER-2/neu non-amplified breast cancers in vivo. Potential implications to long term sensitivity warrants further investigations.

show abstract

“…our experiments demonstrated that EGF transitorily induced EGFR phosphorylation, and EGFR kinase inhibitor, PD153035 inhibited cell migration induced by EGF in human SiHa. It has been well proved that EGFR is an essential regulator in tumorigenesis, including tumor cell migration (Gándola et al, 2014;de Melo Maia et al, 2014;Moerkens et al, 2014). Here we presented the results demonstrating that both EGFR and its kinase activity were required for EGFinduced AQP8 expression and cell migration in human cervical cancer SiHa cells (Figure 3).…”

Section: Discussionmentioning

confidence: 61%

Aquaporin 8 Involvement in Human Cervical Cancer SiHa Migration via the EGFR-Erk1/2 Pathway

Shi¹,

Tuokan²,

Chen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGFinduced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/ Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

show abstract

Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

Cited by 70 publications

References 59 publications

ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells

ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells

Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive/HER-2/neu non-amplified primary breast cancers

Aquaporin 8 Involvement in Human Cervical Cancer SiHa Migration via the EGFR-Erk1/2 Pathway

Contact Info

Product

Resources

About