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Published on: August 11, 2017
Lack of EGF receptor contributes to drug sensitivity of human germline cells
S-J Park1, S Armstrong, C-H Kim
1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. slee@iupui.edu
Abstract:
Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours.
Insights
Germline tumors show high sensitivity to DNA-damaging drugs due to low levels of epidermal growth factor receptor (EGFR). Restoring EGFR increases drug resistance in these cancer cells.
Area of Science:
- Oncology
- Cancer Genetics
- Pharmacology
Background:
- Germline mutations are linked to various tumor types.
- Understanding genetic alterations influencing drug sensitivity is crucial for cancer treatment.
Purpose of the Study:
- To investigate genetic alterations in germline tumors affecting cellular drug sensitivity.
- To explore the role of epidermal growth factor receptor (EGFR) in germline tumor drug response.
Main Methods:
- Testing germline tumor cell hypersensitivity to DNA-damaging drugs.
- Assessing DNA repair activity and protein expression.
- Immunohistochemical analysis of EGFR expression in primary germline tumors.
- Evaluating the effect of EGFR overexpression on drug resistance in germline tumor cells.
Main Results:
- Germline tumor cells exhibited hypersensitivity to DNA-damaging drugs.
- No significant alterations in DNA repair activity or protein expression were found.
- Germline tumors showed significantly lower EGFR expression compared to drug-resistant ovarian cancer cells.
- Overexpression of EGFR in germline tumor cells led to increased drug resistance.
Conclusions:
- A lack of epidermal growth factor receptor (EGFR) contributes to the heightened drug sensitivity of germline tumors.
- EGFR levels are a potential factor influencing therapeutic outcomes in germline cancers.
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