새로운 악성 Brenner 종양 세포주 확립

Abstract

Objective: Ovarian cancer is the most lethal disease among gynecologic malignancies. Although many efforts have been made to explore the mechanisms involved in its development, the genetic events in the pathogenesis of ovarian cancer are still unclear. We characterized a cell line (designated OHK) established from a malignant Brenner tumor cell.

Methods: The cells were obtained during the operation of a 43-year-old Korean woman with ovarian cancer. The OHK cells continuously propagated in vitro over a period of about 36 months and, to date, have undergone over 200 passages, without being infected by either Mycoplasma or any bacteria. We measured the doubling time of OHK cells. To investigate the tumorigenecity of OHK, cells were inoculated subcutaneously into the back of nude mice. Several tumor markers were analyzed using culture media and lysates of cytosol. Morphology and ultrastructure were analyzed by phase-contrast microscopy and electron microscopy. OHK was also analyzed for gene mutation, the typing of human leukocyte antigen and Flow cytometric cell cycle analysis and DNA index.

Results: They proliferated in a monolayered sheet showing a pavement-like arrangement without suppression by intercellular contacts. They also formed epithelial cell lining in shapes of polymorphism and polygons. Doubling time was 38.4 hour which was relatively slow compared to other cancer cells. Microscopic view revealed intranuclear infoldings which are typical in malignant Brenner tumors. The OHK cells secreted significantly high level of CA 125 into the culture medium. A 215th codon at exon 4 of p53 was mutated to C/C in OHK. BRCA 1 was a wild type and polymorphisms were detected in exons 2, 10, 11, 14 and 17 of BRCA 2. The cells showed aneuploidy with DNA index of 1.589 measured by flow cytometry. When transplanted into nude mice, OHK cells successfully induced tumor which was histopathologically resembled malignant Brenner tumor.

Conclusion: These results strongly suggest that OHK is a typical cell line of malignant Brenner tumor. This may provide a useful cellular resource for studying the pathogenesis of malignant Brenner tumor.