Cellular Signaling Pathways in Breast Cancer

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1 ISSN CN / Q http / /cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology ~ 27 DOI /j cnki cjbmb * estrogen receptor ER insulin-like growth factor receptor IGFR epidermal growth factor receptor EGFR ER IGFR EGFR ER IGFR EGFR R736 3 Cellular Signaling Pathways in Breast Cancer SUI Jia-Qi XIE Kun-Peng XIE Ming-Jie * School of Life Sciences Liaoning Normal University Key Laboratory of Biotechnology and Molecular Drug Development of Liaoning Province Dalian Liaoning China Abstract Breast cancer is one of the most common malignant tumor in women Investigation of the occurrence development metastasis and the generation of multi-drug resistance of breast cancer are closely related to the intracellular signaling pathways Estrogen receptor ERα signaling pathway IGFR signaling pathway and EGFR signaling pathway and are particularly important Therefore understanding the mechanism of IGFR ERα EGFR signal pathway and the cross talk between them in depth are very important for seeking the new and more effective targets of tumor treatment This paper mainly reviewed the study of ER IGFR EGFR pathway and the relationship between these three pathways and breast cancer in recent years Key words breast cancer estrogen receptor ER insulin-like growth factor receptor IGFR epidermal growth factor receptor EGFR HER-2 20% ~ 30% 1 Luminal 3 estrogen receptor ER progestrone receptor PR 2 human epidermal growth factor receptor-2 HER-2 4 Luminal A Luminal B HER-2 2 Table 1 Luminal A Luminal B 50% ~ 60% No L No 2013E13SF108 * Tel xmj1222@ sina com Received August Accepted October Supported by Scientific Research Projects of Department of Education Liaoning Province No L and Dalian Municipal Science and Technology Project No 2013E13SF108 tamoxifen TAM selective estrogen receptor modulators SERM * Corresponding author Tel xmj1222@ sina com

2 1 21 HER-2 EGFR tmstuzumab hercepti EGFR DNA HER-2 7 HER-2 4 Luminal B Her-2 HER-2 triple-negative breast cancer TNBC 10% 5 6 EGFR Table 1 Breast cancer classification of molecular subtypes and treatment strategies Classification ER PR HER-2 Treatment strategies Representative drug Luminal A Positive Positive Negative Endocrine therapy TAM Anastrozole Luminal B Positive Positive Positive Endocrine therapy Chemotherapy Targeted therapy Herceptin HER-2 Negative Negative Positive Chemotherapy Herceptin Targeted therapy TNBC Negative Negative Negative Chemotherapy Mitoxantrone ER 13 ERα ERβ ER ER ERα ERβ ERα /ERβ ERα 8 ERβ 9 ER HSP 1 2 ER HSP ER estrogen response element ERE Fuqua ERs 14 ER ERα EGF IGF mrna ERα EGFR IGFR ER Song ERs 15 ERs 12 IGFR HB-EGF

3 22 31 EGFR MAPK insulin-like growth factor binding proteins IGFBPs 3 IGF-ⅠR IGF-ⅡR ER insulin receptor IR IGF-Ⅰ R Kurebayashi 16 IGF-ⅠR 20 ER PR IGF-1 IGF-1R 70% ~ 80% ER PR 10% ERα 150 P-Tyr IRS-1 insulin receptor tamoxifen TAM substrate-1 IRS-1 Tyr ERα 2 P-Tyr ERα36 ERα46 ERα36 36 kd ERα66 2 Ras-MAPK PI3K-Akt / AF-1 AF-2 PKB DNA ERα36 P-Tyr Shc IGF-ⅠR P-Tyr Grb2-SOS IGF-ⅠR ERα66 ERα36 ERα66 PDGF 17 Shi EGF IGF-ⅠR ERα66 ERα36 IGF-ⅡR 2451 ERα ERβ Shaaban ERβ1 2 5 IGF-ⅡR ERβ-2 ERβ IGF- Ⅱ IGF-ⅠR ERβ IGF-1 IGF-1 IGF-1R 2 Worster 22 IGF-I EGF Akt ERK IGF-Ⅰ insulin-like growth factor IGF-ⅠR IGF 2 IGF-1 IGF-II IGF-1R IGF-IIR 7 IGF IGF-Ⅰ IGF-ⅠR

4 % 77 5% EGFR /HerbB1 / 27 5% 25% HER1 HerbB2 / HER2 / Neu HerbB3 / HER3 HerbB4 / Borowiec 24 MCF-7 HER4 29 EGFR 7q IGF-I D1 E 170 kd G 1 S Furukawa 25 IGF-1R mrna IGF-1R HER2 17q kd HER3 /HerbB3 IGF-1 IGF-1R 12q13 mrna 6 2 kb IGF kd 31 HER3 DNA G 1 S IGF-1R HER2 HER2 Carboni HER3 HER2 26 IGF-1R 32 HER4 8 HER2 HER4 Benatar IGFBP-7 G 1 EGFR -1 Dong 28 EGF MCF-7 IGF-1 EGF MAPK PI3 K / AKT EGF HB-EGF IGF-1 α TGF-α 34 EGFR Ras Raf MAPK Src AKT STAT3 /5 35 Ras-Raf-MAPK PI3K-PKC-IKK MAPK PI3K Src /STAT 3 2 EGFR EGFR epidermal growth factor receptor EGFR N EGFR 37 Corkery 38 EGFR EGFR ER PR HER-2

5 24 31 EGFR 42 MCF-7 4 IGF-1R MMPs 2 9 HB-EGF HB-EGF EGFR 48 ER EGFR IGFR ERα IGF-1R IGF-1R IGF-1R IRS-1 IGFBP-3 49 Moore 50 IGF-1 EGF IGF- C50 1 IGF- IGF-1 IGF-1R EGFR 1R IRS-1 IRS-1 IGF-1 EGF EGFR HB-EGF TGFα mrna IGF-1 EGF MAPK IGF-1 EGFR ER COS-7 IGF1R MAPK 43 Castoria 44 cetuximab erbitux gefitinib iressa HerbB2 /Neu IGF-IR PI3K /Akt 20% ~ 30% IGF- 1R 39 HerbB2 IGF-1R ER ER HER2 IGF-1R ER MAPK PI3K / HER2 AKT Kahlert 45 ER HER3 EGFR HER2 IGF-1R Song 46 HER3 ERα Shc IGF1R HER3 MAPK ER Hereguli HER3 IGF-1 ER IGF-1 IGF-1R 40 IGF-1R Shc HER3 PI3K-AKT trans-activating RAS-MAPK EGFR HER2 IGF-1 ER IGF-1R HER3 Chiu E2 ERα 41 EGFR 47 EGFR ERα 4046 HER3 E2 EGF ICI EGF ERα EGFR IGF-1R EGFR MAPK

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