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THY1 expression is associated with tumor suppression of human ovarian cancer
Harindra R Abeysinghe1, Qing Cao, Jia Xu
1Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Abstract:
Microcell-mediated transfer of chromosome 11 into the human ovarian cancer cell line SKOV-3 results in suppression of tumorigenicity in severe combined immunodeficiency (SCID) mice. To identify the differentially expressed transcripts associated with suppression of tumorigenicity, cDNA populations from the slow-growing tumorigenic clone 11(H)8-3, tumorigenic clone 11(H)8-4, and parental SKOV-3 cells were subtracted from the nontumorigenic clones, 11(H)7-2 and 11(C)9-8. The subtracted cDNA populations were either cloned, sequenced and searched in GenBank, or analyzed by gene discovery array screening. A cDNA transcript corresponding to the THY1 gene located at chromosome 11q23 approximately q24 was found to be exclusively expressed in the two nontumorigenic cell clones. In contrast, THY1 expression was not detected in SKOV-3, the tumorigenic hybrid clones, or six other tumorigenic ovarian cancer cell lines. Further analysis using immunocytochemistry and quantitative flow cytometry with a Thy-1-specific antibody confirmed the exclusive expression of THY1 at the protein level in the two nontumorigenic clones. Several cell growth and differentiation-related genes, including thrombospondin 1 (THBS1), SPARC [secreted protein, acidic, cysteine-rich (osteonectin)], and fibronectin (FN1) were also found to be upregulated in the nontumorigenic clones; however, these were expressed in the slow-growing tumorigenic clones as well. Expression of these genes was not observed in the parental SKOV-3 cell line and therefore must be regulated by a gene or genes on chromosome 11. Our results suggest that THY1 is a putative tumor suppressor gene for ovarian cancer and that THBS1, SPARC, and FN1 are genes associated with the regulation of in vivo tumor growth rate.
Insights
Transferring chromosome 11 into ovarian cancer cells suppressed tumor growth. The THY1 gene was exclusively found in non-tumorigenic cells, suggesting it acts as a tumor suppressor gene in ovarian cancer.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Ovarian cancer progression involves complex genetic alterations.
- Tumorigenicity suppression in cancer cell lines is a key area of research.
- Identifying genes responsible for tumor suppression is crucial for therapeutic development.
Purpose of the Study:
- To identify differentially expressed transcripts in ovarian cancer cells after chromosome 11 transfer.
- To investigate the role of specific genes in suppressing ovarian cancer tumorigenicity.
- To explore potential tumor suppressor genes for ovarian cancer.
Main Methods:
- Microcell-mediated chromosome transfer of chromosome 11 into SKOV-3 ovarian cancer cells.
- Subtractive hybridization and cDNA library construction.
- Gene discovery array screening, DNA sequencing, immunocytochemistry, and quantitative flow cytometry.
Main Results:
- The THY1 gene, located on chromosome 11, was exclusively expressed in non-tumorigenic ovarian cancer clones.
- THY1 expression was absent in parental SKOV-3 cells and other tumorigenic ovarian cancer lines.
- Upregulation of thrombospondin 1 (THBS1), SPARC, and fibronectin (FN1) was observed in non-tumorigenic clones, with regulation dependent on chromosome 11.
Conclusions:
- THY1 is a putative tumor suppressor gene in ovarian cancer.
- THBS1, SPARC, and FN1 are associated with regulating in vivo tumor growth rate in ovarian cancer.
- Chromosome 11 transfer effectively suppresses ovarian cancer tumorigenicity, mediated by specific gene expression changes.