The in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma
BACKGROUND: Human epidermal growth factor receptor-2 (Her-2) is over expressed in approximately 25-30% of all primary breast tumors resulting in a distinctive breast cancer subtype associated with a poor prognosis and a decrease in overall survival. Trastuzumab (Herceptin®), an anti-Her-2 monoclonal antibody, has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with primary and acquired resistance.
AIM AND METHODS: To investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium conversion assay), cell cycling (propidium iodide staining), apoptosis (executioner caspases and annexin-V) and relative surface Her-2 receptor expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine potential augmentation of these effects by two endogenous ligands, epidermal growth factor (EGF) and heregulin-β1 (HRG- β1).
RESULTS: Cell viability was decreased in SK-Br-3 cells by exposure to trastuzumab. This was associated with G1 accumulation and decreased relative surface Her-2 receptor density, supporting the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and heregulin-β1 produced differential cell responses alone and in combination with trastuzumab, in some instances augmenting cell viability and cell cycling. Relative surface Her-2 receptor density was reduced substantially by trastuzumab, EGF and heregulin-β1. These reductions were amplified when ligands were used in combination with trastuzumab.
CONCLUSION: Cell type specific interactions of endogenous ligands appear to be dependent on absolute Her-receptor expression and cross activation of signaling pathways. This supports the notion that receptor density of Her-family members and multiplicity of growth ligands are of mutual importance in breast cancer cell proliferation and therefore also in resistance associated with trastuzumab.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2013 |
---|---|
Erschienen: |
2013 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
---|---|
Enthalten in: |
Cancer cell international - 13(2013), 1 vom: 11. Okt., Seite 97 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Hurrell, Tracey [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Completed 15.11.2013 Date Revised 18.03.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.1186/1475-2867-13-97 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM231642784 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM231642784 | ||
003 | DE-627 | ||
005 | 20231224091221.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231224s2013 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1186/1475-2867-13-97 |2 doi | |
028 | 5 | 2 | |a pubmed24n0772.xml |
035 | |a (DE-627)NLM231642784 | ||
035 | |a (NLM)24119761 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Hurrell, Tracey |e verfasserin |4 aut | |
245 | 1 | 4 | |a The in vitro influences of epidermal growth factor and heregulin-β1 on the efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma |
264 | 1 | |c 2013 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 15.11.2013 | ||
500 | |a Date Revised 18.03.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a BACKGROUND: Human epidermal growth factor receptor-2 (Her-2) is over expressed in approximately 25-30% of all primary breast tumors resulting in a distinctive breast cancer subtype associated with a poor prognosis and a decrease in overall survival. Trastuzumab (Herceptin®), an anti-Her-2 monoclonal antibody, has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with primary and acquired resistance | ||
520 | |a AIM AND METHODS: To investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium conversion assay), cell cycling (propidium iodide staining), apoptosis (executioner caspases and annexin-V) and relative surface Her-2 receptor expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine potential augmentation of these effects by two endogenous ligands, epidermal growth factor (EGF) and heregulin-β1 (HRG- β1) | ||
520 | |a RESULTS: Cell viability was decreased in SK-Br-3 cells by exposure to trastuzumab. This was associated with G1 accumulation and decreased relative surface Her-2 receptor density, supporting the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and heregulin-β1 produced differential cell responses alone and in combination with trastuzumab, in some instances augmenting cell viability and cell cycling. Relative surface Her-2 receptor density was reduced substantially by trastuzumab, EGF and heregulin-β1. These reductions were amplified when ligands were used in combination with trastuzumab | ||
520 | |a CONCLUSION: Cell type specific interactions of endogenous ligands appear to be dependent on absolute Her-receptor expression and cross activation of signaling pathways. This supports the notion that receptor density of Her-family members and multiplicity of growth ligands are of mutual importance in breast cancer cell proliferation and therefore also in resistance associated with trastuzumab | ||
650 | 4 | |a Journal Article | |
700 | 1 | |a Outhoff, Kim |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cancer cell international |d 2001 |g 13(2013), 1 vom: 11. Okt., Seite 97 |w (DE-627)NLM118608711 |x 1475-2867 |7 nnns |
773 | 1 | 8 | |g volume:13 |g year:2013 |g number:1 |g day:11 |g month:10 |g pages:97 |
856 | 4 | 0 | |u http://dx.doi.org/10.1186/1475-2867-13-97 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 13 |j 2013 |e 1 |b 11 |c 10 |h 97 |