Objective To discover and identify differentially expressed genes associated with colorectal adenoma formation and the role of Reg IV in colorectal adenoma differentiation.Methods A subtracted cDNA library was constructed with cDNAs that were isolated from either the normal mucosa or adenoma tissue of a single patient. Suppressive subtractive hybridization (SSH) combined with virtual northern blotting was used to characterize differentially expressed genes and contigs were assembled by electronic cloning (in silico cloning) with the EST database. Semi-quantitative RT-PCR was performed in 9 colorectal adenomas.Results The amino acid sequence was determined with open reading frame (ORF) prediction software and was found to be 100% homologous to the protein product of Reg IV (a novel gene isolated from a large inflammatory bowel disease library). RegIV was found to be highly expressed in all of the adenoma samples (9/9) compared with the normal mucosa samples, while 5/6 cases showed Reg IV to be more strongly expressed in adenocarcinoma.Conclusion RegIV may play an important role in the initiation of colorectal adenoma differentiation, and its detection may be useful in the early diagnosis of colorectal adenoma formation.
Guanylin family, described in recent 10 years, is a series of small peptides （including guanylin, uroguanylin and lymphoguanylin） with structural and functional similarities to heat-stable enterotoxins （STs） elaborated by various pathogenic bacteria. They are abundance of cysteines and are endogenous activators of guanylyl cyclase-C （GC-C） receptors. Immunoreactive guanylin family peptides are localized in many human organs and tissues, especially in gastrointestinal tract and kidney, and play an important role in regulation of water and salt homeostasis. Recent studies showed that the mRNA levels of guanylin family peptides were down-regulated in colorectal cancers; oral intake of uroguanylin might suppress polyp formation in Apc（Min/+） mouse, and 111In-labeled-ST peptide analog might specifically target human colon cancers. These evidences highlight that guanylin family may have a potential application in diagnosis and therapy effects of colorectal cancers.
