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Cell Adhes Commun. 1993 Dec;1(3):239-50.

Poorly differentiated colon carcinoma cell lines deficient in alpha-catenin expression express high levels of surface E-cadherin but lack Ca(2+)-dependent cell-cell adhesion.

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1
Laboratory of Cancer Biology, Deaconess Hospital, Harvard Medical School, Boston, MA 02115.

Abstract

Studies on several different types of carcinomas, with the notable exception of colon carcinoma, have shown that poorly differentiated tumors are frequently deficient in E-cadherin dependent cell-cell adhesion. In this study, we examined Ca(2+)-dependent cell-cell adhesion in colon carcinoma cell lines. Five poorly differentiated (Clone A, MIP 101, RKO, CCL 222, CCL 228) and four moderately-well differentiated (CX-1, CCL 235, DLD-2, CCL 187) colon carcinoma cell lines were assayed for their ability to form cell-cell aggregates and for their levels of E-cadherin expression. All of the poorly differentiated cell lines exhibited low levels of Ca(2+)-dependent cell-cell aggregation, in contrast to the moderately-well differentiated cell lines. Contrary to most previous studies, however, we observed that three of the five poorly differentiated cell lines examined expressed E-cadherin by FACS analysis and immunoprecipitation using an E-cadherin mAb. In fact, two of these cell lines expressed a 3- to 4-fold higher level of E-cadherin than that found in the moderately-well differentiated cell lines. mRNA levels for E-cadherin, as evaluated by both RT-PCR and Northern hybridization, corresponded to the levels of protein expression in each of the cell lines. Immunoprecipitation with an E-cadherin mAb, which is known to co-precipitate the catenins, demonstrated that the three poorly differentiated cell lines expressing E-cadherin did not co-precipitate alpha-catenin, although all of the moderately-well differentiated cell lines expressed both alpha- and beta-catenin. RT-PCR confirmed the absence of the alpha-catenin mRNA from two of these cell lines. Stable expression of an alpha-catenin cDNA in one of the poorly differentiated cell lines lacking alpha-catenin expression resulted in a 5-fold increase in its level of Ca(2+)-dependent cell-cell aggregation, providing evidence that alpha-catenin is directly responsible for the loss of cell-cell adhesion in some cell lines. The alpha-catenin transfectants also exhibited a marked reduction in migration on collagen I. These data indicate that loss of alpha-catenin expression, as well as E-cadherin expression, can lead to a phenotype associated with poorly differentiated colon carcinomas.

PMID:
8081881
[Indexed for MEDLINE]

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