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Updated: Sep 27, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Identification of differentially expressed genes in classical and atypical multidrug-resistant gastric carcinoma
Antje Ludwig1, Manfred Dietel, Hermann Lage
1Institute of Pathology, Charité Campus Mitte, Humboldt University Berlin, Schumannstr. 20/21, D-10117 Berlin, Germany.
Abstract:
The phenomenon of multidrug resistance (MDR) in human cancers is the major cause of failure of chemotherapy. To better understand the molecular events associated with the development of different types of MDR, a classical MDR P-glycoprotein expressing gastric carcinoma cell line and an atypical MDR P-glycoprotein-negative variant were analyzed by cDNA array hybridization. Of 588 cDNAs spotted on the array, a total of 9 genes showed differences in mRNA expressions. An enhanced expression level of 3 genes could be detected in both different MDR models (HLH, IR21, CCT5, Tx P-1), 4 genes were overexpressed solely in classical MDR cells (Hsp27, Rcl, aldehyde dehydrogenase 1, vimentin), whereas the expression of one gene was increased in atypical MDR cells (ProTa). Furthermore, the mRNA expressions of 3 genes were down-regulated in atypical MDR cells (Hsp27, vimentin, JNK2), whereas a decrease in mRNA expression in classical MDR cells could be determined for none of them. These differences were confirmed by a semiquantitative RT-PCR approach. Further characterization of these factors may provide more insight into the biology and development of different types of MDR in human gastric carcinomas. Moreover, these genes may be potential candidate factors for the diagnostics and/or prognosis of clinical drug resistance.
Insights
Multidrug resistance (MDR) in cancer hinders chemotherapy. This study identified nine genes with altered expression in gastric cancer cell lines, offering potential diagnostic and prognostic markers for MDR.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a significant obstacle in cancer chemotherapy, leading to treatment failure.
- Understanding the molecular mechanisms underlying different MDR types is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the molecular differences between classical P-glycoprotein-expressing and atypical P-glycoprotein-negative MDR gastric cancer cell lines.
- To identify novel genes associated with the development of MDR in gastric carcinoma.
Main Methods:
- Comparative analysis of gene expression using cDNA array hybridization on 588 cDNAs.
- Validation of differential gene expression using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
Main Results:
- Nine genes exhibited altered mRNA expression levels between the two MDR models.
- Three genes (HLH, IR21, CCT5, Tx P-1) showed enhanced expression in both classical and atypical MDR cells.
- Four genes were overexpressed only in classical MDR cells (Hsp27, Rcl, aldehyde dehydrogenase 1, vimentin), and one in atypical MDR cells (ProTa).
- Three genes (Hsp27, vimentin, JNK2) were downregulated in atypical MDR cells, while none showed downregulation in classical MDR cells.
Conclusions:
- The identified genes represent potential molecular players in the development of distinct MDR phenotypes in gastric cancer.
- These genes may serve as candidate biomarkers for the diagnosis and prognosis of clinical drug resistance in gastric carcinomas.
