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Codominance of cisplatin resistance in somatic cell hybrids
Author(s) -
Ying YuLan Mary,
Shen DingWu,
Liang XingJie,
Gottesman Michael M.
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10320
Subject(s) - cisplatin , hela , cell culture , biology , microbiology and biotechnology , aminopterin , hypoxanthine , somatic cell , genetics , gene , biochemistry , methotrexate , immunology , chemotherapy , enzyme
Abstract Intrinsic or acquired resistance to cisplatin in cancer cells remains a major obstacle to successful chemotherapy. The clinically relevant genetic and molecular mechanisms of resistance have not yet been identified. Cisplatin‐resistant (CP‐r) human KB epidermoid carcinoma cell lines (HeLa) resistant to varying levels of cisplatin after single and multiple selection steps are cross‐resistant to other platinum compounds and to methotrexate. Intraspecies hybrids of the sensitive and KB CP‐r cells were fused with HeLa D98 OR CP‐s, hypoxanthine‐aminopterin‐thymidine (HAT) sensitive, ouabain resistant, to determine whether cisplatin resistance is dominant or recessive. Cell–cell hybridization between the sensitive cells and single‐step or two‐step KB CP‐r cells both indicated codominance of cisplatin resistance compared to hybrids between sensitive cell lines (D98 OR xKB). The hybrids between sensitive cell lines (D98xKB) and a single‐step CP‐r KB cell line (D98xKB‐CP.5) also were cross‐resistant to carboplatin and methotrexate. In addition, the relatively slower growth rate of CP‐r cells appears to be dominant. In the two‐step CP‐r KB cell line, KB‐CP1, resistance is no more dominant than in the single‐step CP‐r KB cell line, KB‐CP.5, suggesting that one of the two steps of resistance in KB‐CP1 may not be dominant. These dominance data suggest that it might be possible to identify one or more genes responsible for cisplatin resistance by gene transfer from a resistant cell line to a sensitive cell line. © 2003 Wiley‐Liss, Inc.