HeLa cell transformants overproducing mouse metallothionein show in vivo resistance to cis-platinum in nude mice

Haruka Toyoda, Tomoe Mizushima, Masahiko Satoh, Narushi Iizuka, Akio Nomoto, Harumi Chiba, Masaharu Mita, Akira Naganuma, Seiichiro Himeno, Nobumasa Imura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Plasmid pSV2MT-I encoding mouse metallothionein-I (MT-I) designed to be expressed under the control of an SV40 promoter was introduced into human HeLa S3 cells. Several transformants (HeLa/MTH) carrying multi-copies of mouse MT-I cDNA in their genomes were isolated. These transformants produced 4 to 20-fold larger amounts of MT than their parent cells. The MT levels in HeLa/MTH were well correlated with the extent of resistance to cadmium, but not with that to cis-platinum (cis-DDP) in vitro. To study the role of MT in resistance to cis-DDP in vivo, nude mice were inoculated subcutaneously with two independent HeLa/MTH clones. MT levels in these tumors were about 3-fold higher than those in the parental cells. The growth of tumors derived from either HeLa/MTH clone was not inhibited in the presence of 15 μmol/kg of cis-DDP, which completely inhibited the growth of tumors derived from the parental HeLa cells. These data strongly suggest that the elevated level of MT confers resistance to cis-DDP in vivo but not in vitro. Thus, the results of this study indicate that in vitro determinations of the influence of MT on cis-DDP resistance may underestimate its importance in in vivo situations.

Original languageEnglish
Pages (from-to)91-98
Number of pages8
JournalJapanese Journal of Cancer Research
Volume91
Issue number1
DOIs
Publication statusPublished - 01-2000

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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