title: Bag-3 expression is involved in pathogenesis and progression of colorectal carcinomas.
abstract: Bcl-2-associated athanogene 3 (Bag-3) belongs to a member of the Hsc70 binding co-chaperone Bag-family proteins and has critical roles in protein homeostasis, cell survival, actin organization, cell adhesion, cell motility and tumor metastasis. To clarify the role of Bag-3 in colorectal carcinogenesis and subsequent development, its expression was examined by immunohistochemistry (IHC) and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adenomas, non-neoplastic mucosa (NNM) and metastatic carcinomas in lymph node and liver. Colorectal carcinoma tissue and cell lines were studied for Bag-3 expression by RT-PCR, Western blot and immunofluorescence. The results demonstrated that Bag3 was distinctly expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620, and WiDr at both mRNA and protein levels. Carcinoma showed stronger Bag-3 expression than adjacent NNM by IHC and Western blot (P<0.05), while its mRNA had the opposite by real-time PCR and ISH (P<0.05). Metastatic carcinoma more frequently expressed Bag-3 mRNA in lymph node and liver than in primary carcinoma (P<0.05). Immunohistochemically, Bag-3 expression was seen to gradually decrease from carcinoma, adenoma to NNM (P<0.05). There was a positive correlation between Bag-3 expression and TNM staging and GRP94 expression (P<0.05), but no relationship to patient age or sex, tumor size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, differentiation or prognosis of colorectal carcinomas (P<0.05). Our study indicated that aberrant Bag-3 expression might be involved in colorectal adenoma-adenocarcinoma sequence and subsequent progression.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Tian
authors.forename: Wen-feng
authors.initials: WF
authors.lastname: Gou
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Xing
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D014408:Biomarkers, Tumor