INFLAMMATORY BOWEL DISEASE Possible role of REG Ia protein in ulcerative colitis and colitic cancer

Background and aims: Although regenerating gene (REG) Ia protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ia gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ia gene expression and whether REG Ia protein has a trophic and/or an antiapoptotic effect on colon cancer cells. Methods: Expression of REG Ia mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ia promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ia protein on growth and H2O2 induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. Results: REG Ia protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ia mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ia promoter activity was enhanced by stimulation with interferon c or interleukin 6. REG Ia protein promoted cell growth and conferred resistance to H2O2 induced apoptosis in LoVo cells. REG Ia protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. Conclusions: The REG Ia gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.