Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-4-23
pubmed:abstractText
Tubular gland structures of colorectal cancer (CRC) have been demonstrated to undergo dedifferentiation at the primary site, and then the gland structures are re-formed in the liver metastases. In this study, we examined the degree of differentiation of the gland structure of 48 cases of CRCs (24 cases with synchronous liver metastasis, 24 cases without metastasis) by the modified Gleason grading system. We also investigated the role of ZO-1, one of the tight junction proteins, in the morphological changes, i.e., dedifferentiation and redifferentiation, of CRCs at the primary site and liver metastases. Liver-metastasized CRCs (2.47+/-0.37) showed a lower score in the modified Gleason grading system than the corresponding primary tumors (3.28+/-0.36) did, i.e., the tumor cells had undergone redifferentiation at liver metastases. ZO-1 was expressed at the apical cell borders of normal colorectal epithelium, the luminal side of which has tubular gland structures. In comparison with this normal epithelium, the ZO-1 expression level was frequently reduced in primary CRC with liver metastasis (20.8%) and ZO-1 was reexpressed in liver metastasized cancers (79.2%). Furthermore, it was demonstrated by an immunoprecipitation-western blotting analysis on 5 cases of CRC with liver metastasis that ZO-1 bound to epidermal growth factor receptor (EGFR) irrespective of the phosphorylation status of EGFR, and that EGFR associated ZO-1 was highly tyrosine-phosphorylated only in the primary CRC, but was dephosphorylated in the liver-metastasized cancers. Our observations suggest that tyrosine phosphorylation of ZO-1 leads to down-regulation of the function of ZO-1 and dedifferentiation of the glands in CRCs, and these phenomena contribute to liver metastases, and redifferentiation of the glands occurs in the liver metastases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
166-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12708492-Adenocarcinoma, pubmed-meshheading:12708492-Adult, pubmed-meshheading:12708492-Aged, pubmed-meshheading:12708492-Aged, 80 and over, pubmed-meshheading:12708492-Cell Differentiation, pubmed-meshheading:12708492-Colorectal Neoplasms, pubmed-meshheading:12708492-Female, pubmed-meshheading:12708492-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12708492-Humans, pubmed-meshheading:12708492-Liver Neoplasms, pubmed-meshheading:12708492-Male, pubmed-meshheading:12708492-Membrane Proteins, pubmed-meshheading:12708492-Middle Aged, pubmed-meshheading:12708492-Neoplasm Proteins, pubmed-meshheading:12708492-Organ Specificity, pubmed-meshheading:12708492-Phosphoproteins, pubmed-meshheading:12708492-Phosphorylation, pubmed-meshheading:12708492-Protein Processing, Post-Translational, pubmed-meshheading:12708492-Receptor, Epidermal Growth Factor
pubmed:year
2003
pubmed:articleTitle
Redifferentiation and ZO-1 reexpression in liver-metastasized colorectal cancer: possible association with epidermal growth factor receptor-induced tyrosine phosphorylation of ZO-1.
pubmed:affiliation
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, 880 Kita-kobayashi, Mibu, Shimotsuga, Tochigi 321-0293.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't