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Tina, Elisabet
Publications (10 of 21) Show all publications
Siekmann, W., Tina, E., Koskela von Sydow, A. & Gupta, A. (2019). Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines. Oncology Letters, 18(1), 395-401
Open this publication in new window or tab >>Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines
2019 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 18, no 1, p. 395-401Article in journal (Refereed) Published
Abstract [en]

Regional anesthesia may prolong survival following surgery for different types of cancers. The mechanisms behind this are unclear but direct effects on cancer cells by local anesthetics (LA) have been suggested. The aim of this study was to investigate if lidocaine or ropivacaine have a dose-dependent effect on the cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro. The colon cancer cell lines SW480 derived from primary tumor and SW620 from a metastatic site in the same patient were exposed to increasing concentrations of lidocaine and ropivacaine (5-1,000 mu M). Cell viability was measured using CellTiter-Blue((R)) and cell proliferation by PKH67 after exposure for up to 72 h. Cell viability was significantly reduced by ropivacaine at the highest concentration (1,000 mu M) after 48 and 72 h in the cell line SW480 and at 72 h in SW620. Exposure to lidocaine did not show any significant reduction in cell viability. Notably, low concentrations of both lidocaine and ropivacaine significantly increased cell viability after 48 and 72 h in SW620. Cell proliferation was significantly reduced by 1,000 mu M lidocaine in SW480 and by 1,000 mu M ropivacaine in SW620. In summary, both lidocaine and ropivacaine showed an anti-proliferative effect in the colon cancer cell lines at high concentrations and after prolonged exposure to LA in vitro. Our findings also indicate that lower concentrations promote cell viability in the metastatic cell line.

Place, publisher, year, edition, pages
Spandidos Publications, 2019
Keywords
local anesthetics, colon cancer, SW480, SW620, in vitro, cell viability, proliferation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-75408 (URN)10.3892/ol.2019.10332 (DOI)000474896900047 ()2-s2.0-85068799738 (Scopus ID)
Note

Funding Agency:

Research Committee of the Örebro County Council

Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-07-30Bibliographically approved
Tina, E., Prosén, S., Lennholm, S., Gasparyan, G., Lindberg, M. & Göthlin Eremo, A. (2019). Expression profile of the amino acid transporters SLC7A5, SLC7A7, SLC7A8 and the enzyme TDO2 in basal cell carcinoma. British Journal of Dermatology, 180(1), 130-140
Open this publication in new window or tab >>Expression profile of the amino acid transporters SLC7A5, SLC7A7, SLC7A8 and the enzyme TDO2 in basal cell carcinoma
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2019 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 180, no 1, p. 130-140Article in journal (Refereed) Published
Abstract [en]

Background: The incidence of basal cell carcinoma (BCC) is increasing and the costs for care rising. Therefore, the need for simplified and cost-effective treatment choices is substantial. Aberrant signalling in several pathways, induced by ultraviolet radiation, is of importance in the development of BCC. Alterations in tumour metabolic activity are part of general carcinogenesis; however, these alterations are only partially recognized in skin cancer.

Objectives: To study expression profiles in BCCs compared with individually matched nontumour skin, with a focus on finding differences associated with tumour metabolism.

Materials and methods: Gene expression in biopsies from BCCs (n = 14) compared with biopsies from nontumour gluteal skin was analysed with microarrays (n = 4 + 4) and/or quantitative real-time polymerase chain reaction (qPCR, n = 14 + 14). Protein expression and localization was assessed using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded BCC samples.

Results: Microarray analysis revealed increased expression of the amino acid transporters SLC7A5, SLC7A7 and SLC7A8 as well as the cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) 2 in BCC. Higher expression of SLC7A5 (P < 0.001), SLC7A8 (P < 0.001) and TDO2 (P = 0.002), but not SLC7A7 (P = 0.50), was confirmed by qPCR, and IHC demonstrated correlating tumour cell protein expression of SLC7A5 and SLC7A8. Protein expression of SLC7A7 was observed in the stratum granulosum, and TDO2 in immune cells.

Conclusions: This study highlights the upregulation of SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply that amino acid transporters may be further explored as potential targets for future medical treatment.

Place, publisher, year, edition, pages
Blackwell Science Ltd., 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:oru:diva-67625 (URN)10.1111/bjd.16905 (DOI)000454745900038 ()29938775 (PubMedID)2-s2.0-85054472080 (Scopus ID)
Note

Funding Agencies:

Lions Cancer Research fund (Region Uppsala Örebro)  

Nyckelfonden (Örebro University Hospital)  

ALF grants, Region Örebro County 

Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2019-01-17Bibliographically approved
Cajander, S., Rasmussen, G., Tina, E., Magnuson, A., Söderquist, B., Källman, J. & Strålin, K. (2018). Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection. PLoS ONE, 13(2), Article ID e0192883.
Open this publication in new window or tab >>Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192883Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-65287 (URN)10.1371/journal.pone.0192883 (DOI)000425604300071 ()29466395 (PubMedID)2-s2.0-85042254936 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council  

ALF research funding (Örebro University)  

Nyckelfonden (Örebro University Hospital)  

ALF research funding (Örebro) 

Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-09-13Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-03-26Bibliographically approved
Siekmann, W., Tina, E. & Gupta, A. (2017). Concentration-dependent cell viability and proliferation in vitro of colon cancer cell lines SW480 and SW620 on exposure to lidocaine or ropivacaine. Acta Anaesthesiologica Scandinavica, 61(8), 1017-1018
Open this publication in new window or tab >>Concentration-dependent cell viability and proliferation in vitro of colon cancer cell lines SW480 and SW620 on exposure to lidocaine or ropivacaine
2017 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1017-1018Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Cancer cells change phenotypes and properties when evolving from primary tumor cells to metastatic cells. These changes might affect the response to local anesthetics (LA). The aim of this study was to investigate if lidocaine or ropivacaine have a dose- dependent effect on cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro.

Methods: The colon cancer cell lines SW 480, derived from primary tumor and SW620 from metastatic tumor in the same patient, were exposed to increasing log-concentrations of lidocaine and ropivacaine. Cell viability was measured using CellTiter Blue, and cell proliferation by PKH67, after exposure for up to 72 h.

Results: Cell viability was not affected after 24 h of exposure. However, the metastatic cell line SW620 showed a significant increase in cell viability at low concentrati ons after 48 and 72 h. Exposure to the higher, but clinically relevant, concentrations of both LA resulted in decreased cell viability in both cell lines. These higher concentrations also showed an inhibitory effect on cell proliferation after 72 h, which was more pronounced for ropivacaine.

Conclusions: Low concentrations of lidocaine and ropivacaine, as achieved in plasma by epidural infusion of LA, do not have direct antiproliferative effects on these colon cancer cell lines in vitro. Higher concentrations of LA, as during continuous local infiltration into tissues over 72 h, inhibit proliferation of both cancer cell lines. The increase in cell viability seen in SW620 should be investigated and underlying mechanisms further elucidated in future studies.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:oru:diva-59281 (URN)10.1111/aas.12941 (DOI)000407231100098 ()
Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2018-08-05Bibliographically approved
Prosén, S., Göthlin Eremo, A., Tsegai, A. D., Lindberg, M. & Tina, E. (2017). Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin. Oncology Letters, 14(2), 2218-2222
Open this publication in new window or tab >>Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin
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2017 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 14, no 2, p. 2218-2222Article in journal (Refereed) Published
Abstract [en]

Basal cell carcinoma is the most common type of cancer in fair-skinned individuals, and its incidence is rapidly increasing. The aim of the present study was to investigate the gene and protein expression of the mitochondrial solute carrier family 25 member 43 (SLC25A43) in basal cell carcinoma. SLC25A43 has previously been identified to be genetically altered and associated with cell proliferation in human epidermal growth factor receptor 2-positive breast cancer. However, the knowledge about SLC25A43 is limited, and its role in other cancers is unknown. The SLC25A43 gene and protein expression was analysed in 14 basal cell carcinomas and healthy skin samples from the same individuals by quantitative polymerase chain reaction and immunohistochemistry, respectively. The results demonstrated a significantly lower (>= 50%) SLC25A43 gene expression in all carcinomas compared with that in healthy skin. In addition, SLC25A43 protein expression was absent in >90% of all visual fields in the basal cell carcinomas, and the H-score was significantly lower in tumours compared with the adjacent epidermis. These results demonstrate that SLC25A43 expression is altered at the gene and protein levels in basal cell carcinoma. The underlying mechanisms and the clinical relevance of these data must be elucidated in additional experimental and clinical studies.

Place, publisher, year, edition, pages
Spandidos Publications, 2017
Keywords
basal cell carcinoma, non-melanoma skin cancer, solute carrier family 25 member 43, quantitative polymerase chain reaction, immunohistochemistry
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-60602 (URN)10.3892/ol.2017.6452 (DOI)000407904600140 ()28781661 (PubMedID)2-s2.0-85021770910 (Scopus ID)
Note

Funding Agency:

Nyckelfonden, Örebro University Hospital Cancer Foundation, Sweden  OLL-255231

Available from: 2017-09-05 Created: 2017-09-05 Last updated: 2019-03-04Bibliographically approved
Kuchalik, J., Magnuson, A. F. .., Tina, E. & Gupta, A. (2017). Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty?: A randomized, double-blind study. BMC Anesthesiology, 17, Article ID 63.
Open this publication in new window or tab >>Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty?: A randomized, double-blind study
2017 (English)In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 17, article id 63Article in journal (Refereed) Published
Abstract [en]

Background: Postoperative inflammation following total hip arthroplasty (THA) can lead to delayed mobilization and return of hip function. Our primary aim was to assess whether local infiltration analgesia (LIA) during surgery can prevent postoperative inflammation.

Methods: This is a sub-analysis of data from a broader double-blind study where 56 patients received spinal anaesthesia for THA. Additionally, Group FNB (Femoral Nerve Block) received an ultrasound-guided femoral nerve block using 30 mL of ropivacaine 7.5 mg/mL (225 mg), and 151.5 mL of saline peri-articularly intra-operatively. Group LIA received 30 mL saline in the femoral nerve block and ropivacaine 2 mg/mL, 300 mg (150 mL) + ketorolac 30 mg (1 mL) + adrenaline 0.5 mg (0.5 mL) peri-articularly. After 23 h, the LIA mixture (22 mL) was injected via a catheter placed peri-articularly in Group LIA and 22 mL saline in Group FNB. A battery of pro-and anti-inflammatory cytokines was assessed using a commercially available kit preoperatively and after 4 h and 3 days postoperatively. Additionally, CRP, platelet count and white blood count was determined pre- and postoperatively.

Results: There was a general trend towards an increase in pro-inflammatory cytokines postoperatively, which returned to normal levels after 3 days. IL-6 concentration was significantly lower 4 h postoperatively in Group LIA compared to Group FNB (p = 0.015). No other significant differences were found between the groups in other cytokines. CRP levels were significantly higher in Group FNB compared to Group LIA 3 days postoperatively (p < 0.001). No other significant differences were seen between the groups.

Conclusion: Local infiltration analgesia has a modest but short-lasting effect on postoperative inflammation in patients undergoing total hip arthroplasty. This is likely to be due to local infiltration of ketorolac and/or local anaesthetics in the LIA mixture. Future studies should be directed towards assessing whether the use of LIA translates into better patient outcomes.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Total hip arthroplasty, Local infiltration analgesia, Postoperative inflammation
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:oru:diva-57862 (URN)10.1186/s12871-017-0354-y (DOI)000400426200001 ()28468607 (PubMedID)2-s2.0-85018738510 (Scopus ID)
Note

Funding Agency:

Research Committee, orebro University HospitaL  OLL-590351

Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2018-08-31Bibliographically approved
Gabrielson, M., Reizer, E., Stål, O. & Tina, E. (2016). Mitochondrial regulation of cell cycle progression through SLC25A43. Biochemical and Biophysical Research Communications - BBRC, 469(4), 1090-1096
Open this publication in new window or tab >>Mitochondrial regulation of cell cycle progression through SLC25A43
2016 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, no 4, p. 1090-1096Article in journal (Refereed) Published
Abstract [en]

An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells.

In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclear Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR.

We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G(1)-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G(1)-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. (C) 2015 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
SLC25A43, Mitochondrial checkpoint, Proliferation, Cell cycle regulation, Ki-67
National Category
Medical Biotechnology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:oru:diva-48760 (URN)10.1016/j.bbrc.2015.12.088 (DOI)000369353000046 ()26721434 (PubMedID)2-s2.0-84957824627 (Scopus ID)
Funder
Swedish Research Council, K2011-54X-20639-04-6
Note

Funding Agencies:

Lion Cancer Foundation Sweden

Research Committee at Örebro County Council

Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2017-11-30Bibliographically approved
Cajander, S., Tina, E., Bäckman, A., Magnuson, A., Strålin, K., Söderquist, B. & Källman, J. (2016). Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis. PLoS ONE, 11(5), Article ID e0154690.
Open this publication in new window or tab >>Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154690Article in journal (Refereed) Published
Abstract [en]

Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, 2016
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-50323 (URN)10.1371/journal.pone.0154690 (DOI)000375676400061 ()27144640 (PubMedID)
Note

Funding Agencies:

Nyckelfonden (Örebro, Sweden)

Research committee of Örebro County Council

Available from: 2016-05-27 Created: 2016-05-16 Last updated: 2018-09-18Bibliographically approved
Göthlin Eremo, A., Tina, E., Wegman, P., Stål, O., Fransén, K., Fornander, T. & Wingren, S. (2015). HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen. International Journal of Oncology, 47(4), 1311-1320
Open this publication in new window or tab >>HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen
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2015 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 47, no 4, p. 1311-1320Article in journal (Refereed) Published
Abstract [en]

The human epidermal growth factor receptor (HER) 4 is a relative of HER2 and has been associated to endocrine breast cancer and prediction of tamoxifen response. In addition to PI3K/Akt and MAPK pathway activation, ligand binding to HER4 triggers proteolytic cleavage and release of an intracellular receptor domain (4ICD) with signaling properties. The aim of the present study was to analyze HER4 protein expression and intracellular localization in breast cancer tissue from patients randomized to treatment with or without adjuvant tamoxifen. To investigate HER4 expression and localization in response to estradiol (E2) and 4-hydroxytamoxifen (4-OHT) exposure, we also performed in vitro studies. Cytoplasmic, nuclear and membrane expression of HER4 protein was evaluated by immunohistochemical staining in tumor tissue from 912 breast cancer patients. Three different breast epithelia cancer cell lines were exposed to E2 and 4-OHT and mRNA expression was analyzed using qPCR. Further, nuclear and cytoplasmic proteins were separated and analyzed with western blotting. We found an association between nuclear HER4 protein expression and ER-positivity (P=0.004). Furthermore, significant association was found between cytoplasmic HER4 and ER-negativity (P<0.0005), PgR-negativity (P<0.0005), tumor size >20 mm (P=0.001) and HER2-negativity (P=0.008). However, no overall significance of HER4 on recurrence-free survival was found. After E2 exposure, HER4 mRNA and protein expression had decreased in two cell lines in vitro yet no changes in nuclear or cytoplasmic protein fractions were seen. In conclusion, nuclear HER4 seem to be co-located with ER, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment. The possible influence of separate isoforms was not tested and future studies may further evaluate HER4 significance.

Place, publisher, year, edition, pages
Athens: Spandidos publications, 2015
Keywords
breast cancer, ErBb4, HER4, randomized patients, tamoxifen
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-45679 (URN)10.3892/ijo.2015.3108 (DOI)000362058300015 ()26238412 (PubMedID)2-s2.0-84941006155 (Scopus ID)
Note

Funding Agencies:

Nyckelfonden, Örebro University Hospital, Sweden

Lions Cancer Research Foundation, Region Uppsala - Örebro, Sweden

Stockholm Cancer Society, Sweden

Available from: 2015-08-31 Created: 2015-08-31 Last updated: 2018-07-01Bibliographically approved
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