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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Expression of the multidrug resistance gene in human tumors
1Department of Surgery, Hiroshima University, Japan.
Abstract:
The expression of MDR1 gene was investigated in human solid tumors with respect to adriamycin resistance. Forty fresh human surgical specimens were analyzed by RNA dot blot assay for their expression of the human MDR1 gene and by immunohistological staining using a monoclonal antibody against P-glycoprotein (MDR1 gene product). The MDR1 mRNA level was increased in 11 cases of 40 cancer patients, including three rectal cancers, two breast cancers, two gastric cancers, one colon cancer, one renal cell carcinoma, one gall bladder cancer and one malignant lymphoma of stomach. However, considerable variation of the MDR1 mRNA level was noted among cancers of a specific type. Immunohistochemical studies with the monoclonal antibody were shown to be positive in 18 tumors. In all tumors tested, the MDR1 mRNA level and the immunohistochemical analysis showed a significant correlation. However, two of five tumors which resisted adriamycin treatment were found to be negative in MDR1 transcript, but positive in immunohistological analysis. These results indicate that immunohistochemical analysis would be more sensitive for detecting P-glycoprotein-expression, and that resistance to adriamycin, being multifactorial, can be associated at least, in part with the increased amount of MDR1 gene product.
Insights
This study investigated the MDR1 gene in human solid tumors and adriamycin resistance. Immunohistochemical analysis for P-glycoprotein showed higher sensitivity than MDR1 mRNA levels in predicting resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- The MDR1 gene, encoding P-glycoprotein, is a key factor in MDR.
- Adriamycin resistance in solid tumors requires better diagnostic markers.
Purpose of the Study:
- To investigate MDR1 gene expression in human solid tumors.
- To correlate MDR1 expression with adriamycin resistance.
- To compare the sensitivity of RNA dot blot and immunohistochemical analysis for P-glycoprotein detection.
Main Methods:
- Analysis of 40 fresh human surgical tumor specimens.
- RNA dot blot assay for MDR1 mRNA expression.
- Immunohistochemical staining using a monoclonal antibody against P-glycoprotein.
Main Results:
- MDR1 mRNA levels were elevated in 11 out of 40 tumors.
- P-glycoprotein expression was detected in 18 out of 40 tumors via immunohistochemistry.
- A significant correlation was observed between MDR1 mRNA levels and P-glycoprotein expression.
- Two adriamycin-resistant tumors showed negative MDR1 transcript but positive P-glycoprotein staining.
Conclusions:
- Immunohistochemical analysis is more sensitive for detecting P-glycoprotein expression than MDR1 mRNA levels.
- Adriamycin resistance is multifactorial and can be partly attributed to increased MDR1 gene product.
- P-glycoprotein expression is a valuable indicator for adriamycin resistance in solid tumors.
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