Related Experiment Videos
Expression of the multidrug-resistance (MDR) gene in breast cancer
M Correnti1, M E Cavazza, N Guedez
1Instituto de Oncología y Hematología, M.S.A.S., Caracas, Venezuela.
Abstract:
Of the approximately 18,000 new cases of cancer in Venezuela each year, only half can be treated with surgery and radiation. The remainder must be treated systematically using chemotherapy or biological response modifiers. It has become evident that any drug resistant human tumors express the MDR1 gene, since MDR1 RNA levels are elevated in many cancers that do not respond to chemotherapy. Human mammary carcinomas have multiple oncogene alterations, the most frequently reported being overexpression of the oncogenes c-myc, int-2, neu and c-myb. Thirteen specimens of mammary cancer were obtained by biopsy of untreated patients in stage IIIB. All these patients received three cycles of FAC or CMF-L+GM-CSF after biopsy. In the slot blot analysis of RNA from invasive carcinomas, MDR1 and c-myc transcripts were detectable at a high level in 30% of tumors. Two patients with increased levels of MDR1 before chemotherapy did not respond to the treatment and distant metastasis and death occurred in these patients. Another patient, MDR1-negative before therapy, did not respond to CMF-1 + GM-CSF and showed high levels of MDR1 transcripts in a second biopsy which was obtained during surgery.
Insights
Elevated multidrug resistance gene 1 (MDR1) RNA levels in breast cancer patients indicate poor response to chemotherapy. High MDR1 expression before treatment predicts treatment failure and metastasis, highlighting its role in drug-resistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Many cancers require systemic treatment like chemotherapy when surgery or radiation is not an option.
- Drug resistance in human tumors is often linked to the multidrug resistance gene 1 (MDR1).
- Elevated MDR1 RNA levels are observed in cancers unresponsive to chemotherapy, suggesting a role in treatment failure.
Purpose of the Study:
- To investigate the correlation between MDR1 gene expression and chemotherapy response in Venezuelan patients with stage IIIB invasive breast cancer.
- To examine the expression of oncogenes c-myc, int-2, neu, and c-myb in relation to treatment outcomes.
Main Methods:
- Biopsy of 13 untreated stage IIIB invasive breast cancer patients.
- Analysis of MDR1 and c-myc RNA transcripts using slot blot analysis.
- Patients received three cycles of FAC or CMF-L+GM-CSF chemotherapy post-biopsy.
Main Results:
- High levels of MDR1 and c-myc transcripts were detected in 30% of the invasive breast carcinoma specimens.
- Two patients with pre-treatment elevated MDR1 levels showed no response to chemotherapy, leading to metastasis and death.
- One patient initially MDR1-negative developed high MDR1 levels during therapy, correlating with a poor response to CMF-1 + GM-CSF.
Conclusions:
- Elevated MDR1 expression before chemotherapy is a significant predictor of poor treatment response and adverse outcomes in invasive breast cancer.
- MDR1 gene expression may play a crucial role in chemotherapy resistance and disease progression in breast cancer patients.
- Monitoring MDR1 levels could potentially guide treatment strategies for breast cancer.