In Vitro pancreatic ductal cell carcinogenesis

Yoshito Ikematsu, Guozhen Liu, Margery A. Fienhold, Martin Cano, Thomas E. Adrian, Michael A Hollingsworth, Janet E. Williamson, Warren Sanger, Tsutomu Tomioka, Parviz M. Pour

Research output: Contribution to journalArticle

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Abstract

Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA-1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N-nitorosobis(2-oxopropyl)amine (BOP). These treated cells were designated TAKA-1 + BOP. The growth of TAKA-1 and TAKA-1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA-1 + BOP was re- cultured in vitro and designated TAKA-1 + BOP-T. Mutation of c-K-ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF-α) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA-1 + BOP but not TAKA-1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non-transformed and transformed cells. TAKA-1, TAKA-1 + BOP and TAKA-1 + BOP-T cells all expressed mRNA of TGF-α and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA-1 nor TAKA-1 + BOP cells has a mutation of c-K-ras or p53. Karyotype analysis demonstrated that TAKA-1 + BOP cells had more chromosomal abnormalities compared with TAKA-1 cells. Mutation of c-K-ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA-1 cells caused expression of TGF-α to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non-transformed and BOP-transformed cells.

Original languageEnglish (US)
Pages (from-to)1095-1103
Number of pages9
JournalInternational Journal of Cancer
Volume72
Issue number6
DOIs
Publication statusPublished - Sep 17 1997

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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