title: Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer.
abstract: Colorectal cancer (CRC) is the most common gastrointestinal type of cancer. The overexpression of Ras proteins, particularly p21Ras, are involved in the development of CRC. However, the subtypes of the p21Ras proteins that are overexpressed and the mutation status remain unknown restricting the development of therapeutic antibodies targeting p21Ras proteins. The present study aimed to investigate the mutation status of ras genes associated with Ras proteins that are overexpressed in CRC and explore whether or not wild-type p21Ras could be a target for CRC therapy. p21Ras expression was examined immunohistochemically in normal colorectal epithelium, benign lesions and malignant colorectal tumor tissues by monoclonal antibody (Mab) KGH-R1 which is able to react with three types of p21Ras proteins: H-p21Ras, N-p21Ras and K-p21Ras. Then, the expression levels of p21Ras subtypes were determined in CRC by a specific Mab for each p21Ras subtype. Mutation status of ras genes in p21Ras-overexpressing CRC was detected by DNA sequencing. There was rare p21Ras expression in normal colorectal epithelium but a high level of p21Ras expression in CRC, with a significant increase from normal colorectal epithelium to inflammatory polyps, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and invasive colorectal adenocarcinoma, respectively. Overexpression of K-p21Ras was found in all CRC tissues tested, overexpression of N-p21Ras was found in 85.7% of the CRC tissues, while H-p21Ras expression was not found in any CRC tissue. DNA sequencing showed that there were no K-ras mutations in 60% of the K-p21Ras-overexpressing CRC, while 40% of the CRC tissues harbored K-ras mutations. N-ras mutations were not found in any N-p21Ras-overexpressing CRC. Our findings indicate that overexpression of wild-type p21Ras may play a prominent role in the development of CRC in addition to ras mutations and could be a promising target for CRC therapy.
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Pathology, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Pathology, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China.
authors.forename: Xin-Yan
authors.initials: XY
authors.lastname: Pan
authors.affiliation: Department of Pathology, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pathology, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China.
authors.forename: Hao-Bin
authors.initials: HB
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Kunming Medical University, Kunming, Yunnan 650031, P.R. China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Hong
authors.affiliation: Department of Pathology, Kunming General Hospital, Kunming, Yunnan 650032, P.R. China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Song
authors.affiliation: Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
authors.forename: Ju-Lun
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)