Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer
Background. It is generally accepted that crosstalk between the growth factor receptor and ER pathways implicated in tamoxifen resistance. The aim of the study was to examine the relationship between mRNA level, protein expression and gene polymorphism of the EGFR/PI3K/AKT signaling components with...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
ABV-press
2018-11-01
|
| Series: | Успехи молекулярной онкологии |
| Subjects: | |
| Online Access: | https://umo.abvpress.ru/jour/article/view/164 |
| _version_ | 1826559135780438016 |
|---|---|
| author | T. A. Dronova N. N. Babyshkina M. V. Zavyalova S. V. Patalyak E. M. Slonimskaya N. V. Cherdyntseva J. G. Kzhyshkowska |
| author_facet | T. A. Dronova N. N. Babyshkina M. V. Zavyalova S. V. Patalyak E. M. Slonimskaya N. V. Cherdyntseva J. G. Kzhyshkowska |
| author_sort | T. A. Dronova |
| collection | DOAJ |
| description | Background. It is generally accepted that crosstalk between the growth factor receptor and ER pathways implicated in tamoxifen resistance. The aim of the study was to examine the relationship between mRNA level, protein expression and gene polymorphism of the EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer. Materials and methods. The study included 95 breast cancer patients who had received adjuvant tamoxifen, of which 31 patients developed recurrence/metastasis after tamoxifen treatment (tamoxifen resistance group), 64 patients did not develop any diseases progression (tamoxifen sensitive group) during the 5 years of follow-up. Genotypes for ESR1 (rs2077647, rs2228480, rs1801132), EGFR (rs1468727, rs2227983), AKT1 (rs1130233) and PTEN (rs11202592) were analyzed using a TaqMan assay. Using reverse transcription-PCR, the relative expression of mRNA for ESR1, EGFR, AKT1 and PTEN was determined. ERα, EGFR, Akt (pS473) and PTEN expression level was evaluated using immunohistochemistry. Progression-free survival (PFS) was estimated by Kaplan – Meier analysis. Results. The minor allele of ESR1 rs2077647 was more prevalent in tamoxifen sensitive tumors compared to tamoxifen resistant tumors (p = 0.044). We found high AKT1 mRNA expression level in tamoxifen sensitive group compared with tamoxifen resistance patients (7.27 ± 5.29 and 0.02 ± 0.01, respectively, p = 0.014). ESR1 rs2228480 was significantly associated with tamoxifen resistance (p = 0.028). EGFR and Akt (pS473) protein expression level was significantly higher in the tamoxifen resistance group compared to tamoxifen sensitive breast cancer patients (p = 0.006 and 0.037, respectively). Patients carrying mutant genotypes of ESR1 rs2228480 had a poorer progression-free survival than those carrying wild and heterozygous variants (log rank p = 0.043). Positive EGFR tumor expression as well as positive Akt (pS473) expression were significantly associated with shorter PFS (log rank p = 0.014 and 0.048, respectively). Conclusion. Polymorphic sites of the ESR1 gene, AKT1 mRNA expression, EGFR expression level and Akt (pS473) protein expression can be potential molecular markers associated with tumor sensitivity/resistance to tamoxifen treatment. |
| first_indexed | 2024-03-12T04:17:46Z |
| format | Article |
| id | doaj.art-261e6561e1974912b715db94c9c95bec |
| institution | Directory Open Access Journal |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| last_indexed | 2025-03-14T08:55:35Z |
| publishDate | 2018-11-01 |
| publisher | ABV-press |
| record_format | Article |
| series | Успехи молекулярной онкологии |
| spelling | doaj.art-261e6561e1974912b715db94c9c95bec2025-03-02T12:45:05ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872018-11-0153405010.17650/2313-805X-2018-5-3-40-50128Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancerT. A. Dronova0N. N. Babyshkina1M. V. Zavyalova2S. V. Patalyak3E. M. Slonimskaya4N. V. Cherdyntseva5J. G. Kzhyshkowska6Саncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityСаncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityСаncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State University; Siberian State Medical UniversityСаncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesСаncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical UniversityСаncеr Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityNational Research Tomsk State University; University of Heidelberg, Mannheim, GermanyBackground. It is generally accepted that crosstalk between the growth factor receptor and ER pathways implicated in tamoxifen resistance. The aim of the study was to examine the relationship between mRNA level, protein expression and gene polymorphism of the EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer. Materials and methods. The study included 95 breast cancer patients who had received adjuvant tamoxifen, of which 31 patients developed recurrence/metastasis after tamoxifen treatment (tamoxifen resistance group), 64 patients did not develop any diseases progression (tamoxifen sensitive group) during the 5 years of follow-up. Genotypes for ESR1 (rs2077647, rs2228480, rs1801132), EGFR (rs1468727, rs2227983), AKT1 (rs1130233) and PTEN (rs11202592) were analyzed using a TaqMan assay. Using reverse transcription-PCR, the relative expression of mRNA for ESR1, EGFR, AKT1 and PTEN was determined. ERα, EGFR, Akt (pS473) and PTEN expression level was evaluated using immunohistochemistry. Progression-free survival (PFS) was estimated by Kaplan – Meier analysis. Results. The minor allele of ESR1 rs2077647 was more prevalent in tamoxifen sensitive tumors compared to tamoxifen resistant tumors (p = 0.044). We found high AKT1 mRNA expression level in tamoxifen sensitive group compared with tamoxifen resistance patients (7.27 ± 5.29 and 0.02 ± 0.01, respectively, p = 0.014). ESR1 rs2228480 was significantly associated with tamoxifen resistance (p = 0.028). EGFR and Akt (pS473) protein expression level was significantly higher in the tamoxifen resistance group compared to tamoxifen sensitive breast cancer patients (p = 0.006 and 0.037, respectively). Patients carrying mutant genotypes of ESR1 rs2228480 had a poorer progression-free survival than those carrying wild and heterozygous variants (log rank p = 0.043). Positive EGFR tumor expression as well as positive Akt (pS473) expression were significantly associated with shorter PFS (log rank p = 0.014 and 0.048, respectively). Conclusion. Polymorphic sites of the ESR1 gene, AKT1 mRNA expression, EGFR expression level and Akt (pS473) protein expression can be potential molecular markers associated with tumor sensitivity/resistance to tamoxifen treatment.https://umo.abvpress.ru/jour/article/view/164estrogen-dependent breast cancertamoxifenegfr/pi3k/akt signalinggene polymorphism |
| spellingShingle | T. A. Dronova N. N. Babyshkina M. V. Zavyalova S. V. Patalyak E. M. Slonimskaya N. V. Cherdyntseva J. G. Kzhyshkowska Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer Успехи молекулярной онкологии estrogen-dependent breast cancer tamoxifen egfr/pi3k/akt signaling gene polymorphism |
| title | Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer |
| title_full | Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer |
| title_fullStr | Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer |
| title_full_unstemmed | Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer |
| title_short | Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer |
| title_sort | relation of egfr pi3k akt signaling components with tamoxifen efficacy in patients with estrogen dependent breast cancer |
| topic | estrogen-dependent breast cancer tamoxifen egfr/pi3k/akt signaling gene polymorphism |
| url | https://umo.abvpress.ru/jour/article/view/164 |
| work_keys_str_mv | AT tadronova relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT nnbabyshkina relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT mvzavyalova relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT svpatalyak relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT emslonimskaya relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT nvcherdyntseva relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer AT jgkzhyshkowska relationofegfrpi3kaktsignalingcomponentswithtamoxifenefficacyinpatientswithestrogendependentbreastcancer |