In vitro pancreatic ductal cell carcinogenesis

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 463 KB
• Volume: 72
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970917)72:6<1095::aid-ijc26>3.0.co;2-2

✦ Synopsis

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-␣) 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-␣ 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-␣ 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. Int.