[6th International Breast Cancer Congress held in Italy].
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Breast Neoplasms↗
Biomedical subjects
Jun Niu
Publications and source records attributed to Jun Niu.
Expressions of p53 and inducible nitric oxide synthase in congenital choledochal cysts.
BACKGROUND: Choledochal cyst, an isolated defect unrestricted to the bile duct, is more appropriately regarded as the sentinel feature of a constellation of anomalies affecting the pancreatobiliary system. This study was to assess the relationship between the expression of inducible nitric oxide synthase (iNOS) and the p53 gene as well as the pathogenesis of choledochal cysts. METHODS: iNOS and p53 were detected by immunohistochemistry staining in 26 patients with congenital choledochal cysts. Histopathologically, hyperplasia of the mucosa of the cysts and the amylase level in the bile were also investigated. RESULTS: Patients with a high level of amylase in the bile had higher expression of iNOS than those with a low level of amylase. p53 protein was expressed neither in fusiform type nor in cystic type. The incidence of mucosal hyperplasia was significantly higher in the fusiform type than that in the cystic type. CONCLUSIONS: Higher expression of iNOS may participate in hyperplasia and carcinogenesis of the mucosa of choledochal cysts. The regurgitation of pancreatic juice into the biliary system might induce mucosal hyperplasia of the biliary tract and inflammatory reaction. In preventing regurgitation-caused hyperplasia and malignancy of the bi-liary tract, early surgery is important for children with congenital choledochal cysts.
Adolescent↗
Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the beta6 integrin subunit.
We have previously reported that the alphavbeta6 integrin upregulates its own expression in a protein kinase C-dependent manner with increasing cell density. The wild-type beta6 integrin subunit has also been shown to promote tumour growth in vivo and its growth-enhancing effect is regulated by both a MAP kinase binding motif on beta6 and the 11 amino acid C-terminal cytoplasmic extension unique to the beta6 subunit. Herein, we show that the 11 amino acid cytoplasmic extension is essential for the cell density-dependent increase in beta6 expression and that the 11 amino acid tail exerts a dominant negative effect on cell density- and PKC-mediated beta5 expression in alphavbeta6-expressing colon cancer cells. Cells that express beta6 lacking the 11 amino acid tail respond to PKC simulation with increased expression of only the beta5 subunit as seen for cells that lack constitutive alphavbeta6 expression. In contrast, loss of the ERK binding site on beta6 markedly impairs cell density- and PKC-dependent expression of either beta6 or beta5 in the presence or absence of the 11 amino acid tail, respectively. Our findings suggest that in alphavbeta6-expressing cells, a hierarchy of kinase signalling cascades exists and that the beta6-ERK2 interaction dominates over PKC-mediated signalling pathways responsible for integrin upregulation with cell confluence. Given the dominance of the beta6-ERK2 interaction over PKC-mediated expression of both beta5 and beta6 integrin subunits, targeting the beta6-ERK2 interaction may prove useful as an anticancer strategy in colon cancer.
Amino Acid Motifs↗
Direct integrin alphavbeta6-ERK binding: implications for tumour growth.
Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In alphavbeta6-expressing cells ERK2 is bound only to the beta6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by beta6-bound ERK. Deletion of the ERK2 binding site on the beta6 cytoplasmic domain inhibits tumour growth and leads to an association between ERK and the beta5 subunit. The physical interaction between integrin alphavbeta6 and ERK2 defines a novel paradigm of integrin-mediated signalling and provides a therapeutic target for cancer treatment.
Amino Acid Sequence↗