Cytokeratin expression during AFB₁-induced carcinogenesis

Abstract

The early stages of the carcinogenic process induced by aflatoxin B1 (AFB1) in rat liver during 24 weeks of feeding and the resulting tumours have been studied with respect to cytokeratin (CK) expression. A previously uncharacterized monoclonal antibody, MRCTU/J1, has been shown to recognize rat CK18 and together with antibodies against human CK8, 18 and 19, has been used to examine the possible lineage of tumour cells and also to identify the altered foci that might be most relevant to tumorigenesis. Results suggested that AFB1-induced transformation in liver may occur in more than one cell type, since tumours with the normal hepatocyte CK pattern and those with bile duct or oval cell CK phenotype were identified. Additionally, hepatocytes with a bile duct CK phenotype appeared during the early stages of carcinogenesis. The in vivo pattern of CK expression also appeared to be maintained in one normal and one hepatoma-derived cell line. Overexpression of CKs (particularly of CK19) was a much more selective marker for altered foci, compared to gamma-glutamyltranspeptidase, and was more consistently expressed at high levels in tumours, suggesting that it might be a more reliable way of identifying those cells involved in the transformation process.

From Proteomic Analysis to Clinical Significance

“…Such observations suggest that CK19-positive tumor cells might invade normal tissues more easily and gain access to the circulation, thus harboring the risk of tumor recurrence. CK19 expression was also found to be related to poor differentiation in agreement with previous reports in HCC (31,32).…”

EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

“…Both T-Plastin and Caldesmon are actin bundling proteins, and expression of such cytoskeletal proteins have been widely reported to be correlated with oncogenic phenotypes (Green et al, 1990;Davies et al, 1993;De Silva et al, 1994). Tplastin, one of three plastin isoforms, is upregulated up to 12-fold in cisplatin-resistant tumor cells by comparison to their parental non-resistant cells, and the expression of antisense T-plastin RNA restores cisplatin sensitivity (Hisano et al, 1996).…”

Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

“…Immunohistochemistry was performed on acetone-fixed rat liver sections as described previously [32,33], using the same polyclonal antibodies against either human GST T1-1 or rat GST T2-2 (diluted 1 : 250) that were employed in the Western blotting experiments, and alkaline phosphatase-conjugated secondary antibodies obtained from Bio-Rad Laboratories (diluted 1 : 100).…”