Identification and sequencing of the Syrian Golden hamster (Mesocricetus auratus) p16INK4a and p15INK4b cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells

Peter Muscarella, Thomas J. Knobloch, Alexis B. Ulrich, Bruce C. Casto, Nicolas Moniaux, Uwe A. Wittel, W. Scott Melvin, Parviz M. Pour, Huijuan Song, Barry Gold, Surinder K. Batra, Christopher M. Weghorst

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Previous studies have shown that the p16INK4a tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15INK4b gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden hamster (Mesocricetus auratus) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16INK4a and p15INK4b genes in two experimental hamster models for human pancreatic and oral carcinogenesis. First, hamster p16INK4a and p15INK4b cDNAs were cloned and sequenced. The hamster p16INK4a cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16INK4a sequences, respectively. Similarly, the hamster p15INK4b cDNA ORF shares 82% and 89% sequence identity with human and mouse p15INK4b, respectively. Second, a deletion analysis of hamster p16INK4a and p15INK4b genes was performed for several tumorigenic and non-tumorigenic hamster cell lines and revealed that both p16INK4a and p15INK4b were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16INK4a and p15INK4b genes plays a prominent role in hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalGene
Volume278
Issue number1-2
DOIs
StatePublished - Oct 31 2001
Externally publishedYes

Keywords

  • Adenocarcinoma
  • Buccal
  • Head and neck
  • Pancreas
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Genetics

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