HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin
Breast tumor cells overexpressing the proto-oncogene HER2/neu are known to be less responsive to certain DNA-binding chemotherapeutic agents. The current study specifically investigates the correlation between chemosensitivity to the DNA-binding drug doxorubicin and cellular HER2/neu protein levels...
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| Format: | Article |
| Language: | English |
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McGill University
2020-12-01
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| Series: | McGill Journal of Medicine |
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| Online Access: | https://mjm.mcgill.ca/article/view/673 |
| _version_ | 1818664763562917888 |
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| author | Anne Mullin Bertrand Jean-Claude |
| author_facet | Anne Mullin Bertrand Jean-Claude |
| author_sort | Anne Mullin |
| collection | DOAJ |
| description | Breast tumor cells overexpressing the proto-oncogene HER2/neu are known to be less responsive to certain DNA-binding chemotherapeutic agents. The current study specifically investigates the correlation between chemosensitivity to the DNA-binding drug doxorubicin and cellular HER2/neu protein levels in a panel of eight breast cancer cell lines (HS-578, BT-474, MDA-MB-453, MDA-MB-231, MDA-MB-175, MCF-7, ZR-75-1 and T47D). The IC50 (the drug concentration required to inhibit cell growth by 50%) values for the cell lines were determined by the sulforhodamine B assay. IC50 values were correlated with HER2/neu protein levels determined by Western blotting. An almost linear relationship between IC50 and HER2/neu protein level for seven cell lines (p = 0.02, r2 = 0.680) was found, with protein levels increasing as resistance increased. The findings suggest that overexpression of HER2/neu correlates with increased resistance to doxorubicin in seven of eight breast cancer cell lines studied. The observation that, in one cell line (MDA-MB-175), doxorubicin IC50 did not correlate with HER2/neu levels, suggests that in these cells, an as-of-yet unidentified factor contributes to resistance. If the observed correlation, which was present in seven of eight cell lines, is confirmed in a larger sample size, increased HER2/neu levels may be implemented as a predictor of breast tumor sensitivity to doxorubicin. |
| first_indexed | 2024-12-17T05:37:55Z |
| format | Article |
| id | doaj.art-351b4181b44f485faa3dd8f9ef0b9c77 |
| institution | Directory Open Access Journal |
| issn | 1715-8125 |
| language | English |
| last_indexed | 2024-12-17T05:37:55Z |
| publishDate | 2020-12-01 |
| publisher | McGill University |
| record_format | Article |
| series | McGill Journal of Medicine |
| spelling | doaj.art-351b4181b44f485faa3dd8f9ef0b9c772022-12-21T22:01:33ZengMcGill UniversityMcGill Journal of Medicine1715-81252020-12-014110.26443/mjm.v4i1.673888HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug DoxorubicinAnne MullinBertrand Jean-ClaudeBreast tumor cells overexpressing the proto-oncogene HER2/neu are known to be less responsive to certain DNA-binding chemotherapeutic agents. The current study specifically investigates the correlation between chemosensitivity to the DNA-binding drug doxorubicin and cellular HER2/neu protein levels in a panel of eight breast cancer cell lines (HS-578, BT-474, MDA-MB-453, MDA-MB-231, MDA-MB-175, MCF-7, ZR-75-1 and T47D). The IC50 (the drug concentration required to inhibit cell growth by 50%) values for the cell lines were determined by the sulforhodamine B assay. IC50 values were correlated with HER2/neu protein levels determined by Western blotting. An almost linear relationship between IC50 and HER2/neu protein level for seven cell lines (p = 0.02, r2 = 0.680) was found, with protein levels increasing as resistance increased. The findings suggest that overexpression of HER2/neu correlates with increased resistance to doxorubicin in seven of eight breast cancer cell lines studied. The observation that, in one cell line (MDA-MB-175), doxorubicin IC50 did not correlate with HER2/neu levels, suggests that in these cells, an as-of-yet unidentified factor contributes to resistance. If the observed correlation, which was present in seven of eight cell lines, is confirmed in a larger sample size, increased HER2/neu levels may be implemented as a predictor of breast tumor sensitivity to doxorubicin.https://mjm.mcgill.ca/article/view/673her2/neu oncogenebreast cancerdoxorubicin |
| spellingShingle | Anne Mullin Bertrand Jean-Claude HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin McGill Journal of Medicine her2/neu oncogene breast cancer doxorubicin |
| title | HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin |
| title_full | HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin |
| title_fullStr | HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin |
| title_full_unstemmed | HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin |
| title_short | HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin |
| title_sort | her2 neu oncogene and sensitivity to the dna interactive drug doxorubicin |
| topic | her2/neu oncogene breast cancer doxorubicin |
| url | https://mjm.mcgill.ca/article/view/673 |
| work_keys_str_mv | AT annemullin her2neuoncogeneandsensitivitytothednainteractivedrugdoxorubicin AT bertrandjeanclaude her2neuoncogeneandsensitivitytothednainteractivedrugdoxorubicin |