Evaluation of the malignant potential of aberrant crypt foci by immunohistochemical staining for beta-catenin in inflammation-induced rat colon carcinogenesis.
We previously showed that colitis enhanced the development of cancer and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in Fischer 344 rats. In this study, we examined the effect of two different anti-inflammatory drugs [non-steroidal anti-inflammatory drugs (NSAIDs: Fenbufen) and a platelet activating factor-receptor antagonist (PAF-RA)] on the inflammation-induced rat colon carcinogenesis. Furthermore, we examined the expression and the localization of beta-catenin protein, and the proliferating cell nuclear antigen (PCNA)-labeling index (LI) in ACF and cancer. PAF-RA significantly decreased the incidence of ACF in the rats (p<0.05), but Fenbufen did not affect the incidence of ACF and cancer. In most of the ACF (91%), beta-catenin was localized at the cell membrane like in normal colon epithelium. In about 9% of the ACF, beta-catenin was overexpressed not only on the cell membrane but also in the cytoplasm. In all of the cancer cells, beta-catenin was overexpressed in the nucleus. When we compared the PCNA-LI in the ACF showing normal beta-catenin expression pattern with that in the ACF showing abnormal beta-catenin expression pattern (overexpression in cytoplasm), there was no significant difference of the PCNA-LI in these two different types of ACF. These findings suggest that immunohistochemical staining of ACF for beta-catenin can evaluate the malignant potential of ACF, and that PAF-RA can be used for preventing the development of ACF in inflammation-induced carcinogenesis.
Furihata
Tadashi
T
Department of Gastroenterological Surgery, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
Kawamata
Hitoshi
H
Kubota
Keiichi
K
Fujimori
Takahiro
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D014408:Biomarkers, Tumor; D002455:Cell Division; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010654:Phenylbutyrates / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D010654:Phenylbutyrates; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D051176:beta Catenin; C039351:platelet activating factor receptor; C010725:fenbufen