ABSTRACT
Abnormal activation of Wnt signaling pathway is closely related to the occurrence of tumor, and T cell factor 4 (Tcf4 ) and beta-catenin are important signal transmission factors of this pathway. The aim of the present study is to explore the significance and correlation between expression of Tcf4, beta-catenin and secreted frizzled related protein 1(SFRP1), suppressor gene of Wnt signaling pathway, in colorectal carcinoma and their correlations to the clinicopathological factors. The expressions of Tcf4, beta-catenin and SFRP1 were performed with immunohistochemistry staining in 97 cases of primary colorectal carcinoma and 40 cases of normal colorectal mucosa tissues. The results showed that the abnormal expression rates of Tcf4 and beta-catenin in colorectal carcinoma were significantly higher than those in the control groups (P<0.01). The positive rate of SFRP1 was significantly lower than those in the control groups (P<0.01). The abnormal expression rates of Tcf4 and beta-catenin were also related to the lymph node metastasis and Dukes stage (P<0.05). A significant correlation was found between the expressions of SFRP1 and Tcf4, beta-catenin (P<0.05). Overexpression of Tcf4 and beta-catenin was related to poor prognosis (P<0.05). But the survival rates of the group with SFRP1 expressions were higher than those in group without SFRP1 expressions (P<0.05). Cox multifactor regression analysis indicated that Dukes stage, expression of beta-catenin and SFRP1 were independent risk factors of colorectal carcinoma (P<0.05). The results suggested that the abnormal expression of Tcf4 and beta-catenin in colorectal cancer may be related to the reduced or absent expression of SFRP1. beta-catenin accumulation in the nuclei formed complexes with Tcf4 is one of the important molecular switch maintaining colorectal malignant phenotype. The combined detection of these indexes may perform an important role in predicting the progression and prognosis of colorectal cancer, and could provide new molecular targets for gene treatment of colorectal cancer.
Subject(s)
Humans , Carcinoma , Metabolism , Colorectal Neoplasms , Metabolism , Disease Progression , Intercellular Signaling Peptides and Proteins , Metabolism , Lymphatic Metastasis , Membrane Proteins , Metabolism , Phenotype , Prognosis , Risk Factors , Transcription Factor 7-Like 2 Protein , Metabolism , Wnt Signaling Pathway , beta Catenin , MetabolismABSTRACT
Objective To elucidate the mechanism of SSA/Ro formation after UV exposure,and its significance in the pathogenesis of photosensitive LE skin lesion.Methods Human keratinocytes(HKC)were cultured in Medium-154.After ultraviolet-B light(UVB)irradiation,the morphological change of apoptotic HKC was observed under phase contrast microscopy,the DNA fragment of apoptotic cell was de-tected by in situ nick end-labeling.And the expression of SSA/Ro was detected by indirect immunofluores-cence(IIF).As target cells,UVB irradiated keratinocytes were incubated with affinity-purified anti-SSA/Ro sera,with or without freshly prepared human sera.SSA/Ro antigen from supernatant of irradiated ker-atinocytes was also detected with an ELISA method.Results The treatment of keratinocytes with serial dos-es(52.8mJ/cm 2 ?105.6mJ/cm 2 ?158.4mJ/cm 2 ?200mJ/cm 2 ?211mJ/cm 2 )of UVB induced SSA/Ro expression on cell membrane and apoptosis,leading to apoptotic bleb formation on cell surface,which were proved con-taining SSA/Ro and ribonucleoprotein.SSA/Ro antigen expressed on UVB irradiated keratinocytes was proved to be bound to affinity purified anti-SSA/Ro sera and lead to complement-depend cytotoxicity.But no SSA/Ro in supernatant was detected.Conclusions UVB irradiation induces SSA/Ro expression on the HKC sur-face through apoptosis,and no SSA/Ro antigen was found in supernatant.The result suggests that SSA/Ro anti-gen expressed on UVB irradiated keratinocytes could be recognized and presented to immune cells by direct cell-cell contact.