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A multidrug-resistant ovarian carcinoma cell line with a malignant suppressed phenotype is a CD44 gene expression
J R Teyssier1, P Couillin, J Bénard
1Cytogenetics Laboratory, Faculty of Medicine, INSERM U314, Reims, France.
Abstract:
A multidrug-resistant cell subline (OV1/VCR) derived from an ovarian adenocarcinoma cell line (OV1/P) was characterized by a typical suppressed malignant phenotype and by a unique karyotypic change: del(11)(p13). In an attempt to discern some genetic alteration of 11p genes that may be relevant to the phenotypic shift, cells were analyzed with DNA probes mapped in the deleted region and with monoclonal antibodies (MoAbs) against 11p-encoded membrane molecules. Southern blot did not detect abnormal restriction patterns of the probed sequences. OV1/VCR cells did not express the CD44 epitope (11p13 MIC4 locus) recognized by the F10-44 MoAb and did not accumulate RNAs of the CD44 (Hermes) core peptide. This defect was not detected in another OV1/P-derived drug-resistant subline that retained the malignant behavior and did not have the del(11p) marker. It may have contributed to phenotypic reversion because evidence shows that CD44 membrane molecule is involved in cell-cell interaction and growth regulation of cancer cells.
Insights
Multidrug-resistant ovarian cancer cells (OV1/VCR) showed a suppressed malignant phenotype and a deletion on chromosome 11p13. This was linked to the loss of CD44 (Hermes) expression, potentially impacting cell interactions and growth regulation.
Area of Science:
- Oncology
- Cancer Genetics
- Molecular Biology
Background:
- Ovarian adenocarcinoma cell lines provide models for studying drug resistance and cancer progression.
- Multidrug resistance in cancer is often associated with complex genetic alterations and phenotypic changes.
- Specific chromosomal regions, such as 11p13, can harbor genes critical for cancer cell behavior.
Purpose of the Study:
- To investigate genetic alterations in the 11p13 region of a multidrug-resistant ovarian cancer cell subline (OV1/VCR).
- To determine the role of specific 11p genes, particularly CD44, in the suppressed malignant phenotype of OV1/VCR cells.
- To correlate karyotypic changes with molecular defects and phenotypic reversion in drug-resistant cancer cells.
Main Methods:
- Karyotypic analysis to identify chromosomal abnormalities, specifically del(11)(p13) in OV1/VCR cells.
- Southern blot hybridization to detect alterations in DNA sequences within the deleted 11p13 region.
- Immunophenotyping using monoclonal antibodies (MoAbs) to assess expression of 11p-encoded membrane molecules, including CD44 (MIC4 locus).
- RNA analysis to investigate the accumulation of CD44 (Hermes) core peptide RNAs.
Main Results:
- The multidrug-resistant OV1/VCR cell subline exhibited a suppressed malignant phenotype and a specific karyotypic change, del(11)(p13).
- Southern blot analysis did not reveal abnormal restriction patterns for probed sequences within the deleted region.
- OV1/VCR cells showed a complete absence of CD44 epitope expression (MIC4 locus) and did not accumulate CD44 (Hermes) core peptide RNAs.
- This CD44 expression defect was specific to OV1/VCR cells and not observed in another drug-resistant subline lacking the del(11p) marker and retaining malignant behavior.
Conclusions:
- The del(11)(p13) chromosomal abnormality in OV1/VCR cells is associated with a loss of CD44 (Hermes) expression.
- The absence of CD44 expression may contribute to the observed phenotypic reversion and suppressed malignancy in this multidrug-resistant ovarian cancer subline.
- CD44, a molecule involved in cell-cell interactions and growth regulation, is a potential key factor in the altered behavior of drug-resistant ovarian cancer cells.