Immunohistochemistry of DNA fragmentation factor in human stomach and colon: Its correlation to apoptosis

Hideyuki Sasaki, Takashi Suzuki, Nobuo Funaki, Tatsuya Hoshi, Masahiro Iwabuchi, Ryoji Ohi, Hironobu Sasano

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

DNA fragmentation factor (DFF) is an important factor in the pathway leading to apoptosis, which is activated by caspase-3 and is involved in the formation of nuclear DNA fragments. DFF is a heterodimic protein of 40 kDa and 45 kDa that becomes activated when DFF is cleaved by caspase-3. Of the two enzymatically cleaved fragments of DFF, it is the 40 kDa fragment (DFF40) that is the active component of DFF and is responsible for triggering chromatin condensation when incubated with nuclei. However, the topological correlation between apoptosis and DFF expression in human tissues has not been examined. Therefore, in this study, we first immunolocalized DFF in non-neoplastic mucosa, hyperplastic polyp, adenoma and carcinoma of human stomach and colon. We then examined apoptosis in serial tissue sections. Labeling index (LI) of DFF and TUNEL positive cells in the same areas of serial tissue sections were obtained using computer-assisted image analysis. In the stomach, the DFF LI in non-neoplastic mucosa (9.8 ± 5.0%, n = 3) and carcinoma (18.2 ± 3.6, n = 3) were significantly lower than that of hyperplastic polyp (73.3 ± 9.2%, n = 3) and adenoma (66.5 ± 18.3%, n = 3) [p < 0.0001]. In colon, the DFF LI in non-neoplastic mucosa (10.2 ± 6.4%, n = 3) was significantly lower than that of hyperplastic polyp (56.0 ± 34.7%, n = 3) [p = 0.0013] and adenoma (30.1 ± 16.3%, n = 3) [p = 0.0037]. Cells positive for DFF were much more widely distributed than TUNEL positive cells in both non-pathologic and pathologic mucosa of human stomach and colon. Notably, DFF positive cells were present beneath the TUNEL positive cells in non-pathological gastric and colonic epithelium. In addition, there was a significant positive correlation between DFF and TUNEL LIs in human stomach and colon [p < 0.0001]. These results suggest that DFF may be involved in the process of apoptosis in human gastric and colonic mucosa.

Original languageEnglish
Pages (from-to)5277-5282
Number of pages6
JournalAnticancer research
Volume19
Issue number6 B
Publication statusPublished - 1999 Nov

Keywords

  • Apoptosis
  • Colon
  • DNA fragmentation factor
  • Immunohistochemistry
  • Stomach

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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