Catenins, a, b, g

a-catenin: Becton Dickinson (1G5) and Transduction Laboratories.
b-catenin: Transduction Laboratories and Zymed (5H10).
g-catenin: Becton Dickinson (10C4) and Transduction Laboratories.

HIER is necessary for the immunoreactivity of these antibodies in fixed paraffin-embedded sections. Immunoreactivity is preserved in frozen sections and cell preparations.

There is currently a great deal of interest in the adhesion molecules and their expression and localization. Cell-to-cell adhesion plays a major role not only in embryogenesis but also in the intercellular adhesion of cancer cells and hence their motility and metastasis (Jiang 1996; Ilyas & Tomlinson, 1997). The transmembrane molecule E-cadherin is considered to be one of the key molecules in the formation of the intercellular junctional complex and establishment of polarity in epithelial cells. The cytoplasmic domain of E-cadherin in adherens junctions interacts via intracellular catenins with the actin-based cytoskeleton and includes fodrin, whereas the extracellular domain is involved in homotypic cell-to-cell adhesion through the formation of a molecular zipper complex. The integrity of the E-cadherin adhesion system has been shown to be disturbed or disrupted in experimental and human carcinomas and reduced expression of E-cadherin induces dedifferentiation and invasiveness in tumor cells (Tsukita et al, 1992; Birchmeier & Behrens, 1994; Ilyas & Tomlinson, 1997).
Catenins, the a-subunit (102 kD), b-subunit (88 kD) and g-subunit (82 kD), are a group of proteins that interact with the intercellular domain of E-cadherin, resulting in complexes of E-cadherin/b-catenin/a-catenin or E-cadherin/g-catenin/a-Catenin (Hinck et al, 1994). a-Catenin shows sequence homology to vinculin and interacts with the actin cytoskeleton, either directly or indirectly via a-actinin;b-catenin is the vertebrate homologue of the Drosophila segment polarity gene armadillo; and g-catenin, which is identical to plakoglobin, is also found in desmosomes (Jiang, 1996). The regions of both a- and b-catenin, located on 5q21-22 and 3p21, have been shown to be involved in the development of certain tumors (see Jiang, 1996) and reduced expressions of botha- and b-catenin have been described in various tumors including breast carcinoma (Hashizume et al, 1996). Besides adhesion functions, b-catenin binds to APC (adenomatous polyposis coli) protein, a putative tumor suppressor. APC mutation disturbs the equilibrium and levels of freeb-catenin level in the cell and may have a role in tumorigenesis.b-catenin has recently been shown to have a function in signal transduction when bound with members of the Tcf-LEF family of DNA-binding proteins (Behrens et al, 1996).

Although currently not of diagnostic importance, the expression of the catenin proteins and their localization are potentially important markers to predict motility and invasiveness of epithelial neoplasms (Sormunen et al, 1998). Our studies suggest that the detachment ofb-catenin from the cell membrane heralds the breakdown of the cadherin-catenin-fodrin-cytoskeletal complex both in vitro and in vivo. The loss of cell-to-cell adhesion is concomitant with a change in cell shape, from epithelioid to fibroblastoid (Sormunen et al, 1998).

The monoclonal antibodies from Transduction Laboratories are immunoreactive in routinely fixed, paraffin-embedded tissue section but only following HIER in citrate buffer.

•Berhens J, Von Kries JP, Kuhl M et al 1996. Functional interaction of beta-catenin with the transcriptional factor LEF-1. Nature 384:638-642.

•Birchmeier W, Behrens J 1994. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochemia Biophysiology Acta 1198: 11-26.

•Hashizume R, Koizumi H, Ihara A et al 1996. Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alphacatenin. Histopathology 29: 139-146.

•Hinck L, Nathke IS, Papkoff J, Nelson WJ 1994. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. Journal of Cell Biology 125: 1327-1340.

•Ilyas M, Tomlinson IPM 1997. The interactions of APC, E-cadherin andb-catenin in tumour development and progression. Journal of Pathology 182: 128-137).

•Jiang WG 1996. E-cadherin and its associated protein catenins, cancer invasion and metastasis. British Journal of Surgery 83:437-446.

•Sormunen RT, Leong AS-Y, Vaaraniemi JP et al 1998. Fodrin, E-cadherin andb-catenin immunolocalization in infiltrating ductal carcinoma of the breast correlated with selected prognostic indices. Journal of Pathology (submitted)

•Tsukita S, Nagafuchi A, Yonemura S 1992. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Current Opinion in Cell Biology 4:834-839.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.