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 - 2000 Jan

Keywords

  • Drug resistance
  • HeLa cell
  • Metallothionein
  • Overexpression
  • cis-platinum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'HeLa cell transformants overproducing mouse metallothionein show in vivo resistance to cis-platinum in nude mice'. Together they form a unique fingerprint.

  • Cite this

    Toyoda, H., Mizushima, T., Satoh, M., Iizuka, N., Nomoto, A., Chiba, H., Mita, M., Naganuma, A., Himeno, S., & Imura, N. (2000). HeLa cell transformants overproducing mouse metallothionein show in vivo resistance to cis-platinum in nude mice. Japanese Journal of Cancer Research, 91(1), 91-98. https://doi.org/10.1111/j.1349-7006.2000.tb00864.x