VACUOLAR APICAL COMPARTMENT (VAC) IN BREAST-CARCINOMA CELL-LINES (MCF-7 AND T47D) - FAILURE OF THE CELL-CELL REGULATED EXOCYTOSIS MECHANISMOF APICAL MEMBRANE

We have previously shown that an integral plasma membrane glycoprotein (AP2) is highly polarized to the apical domain in confluent Madin-Dar by canine kidney (MDCK) epithelial cells. However, when the monolayers are prevented from forming intercellular contacts, approximately 60% of the AP2 cellular content is stored in the intracellular vacuolar ap ical compartment (VAC). In the current work we found that AP2 was pres ent in the non-tumorigenic human mammary epithelial cell line MCF-10A, in the breast carcinoma cell lines MCF-7 and T47D, and in breast duct al carcinomas in vivo. By radioimmunoassay, an intracellular compartme nt of AP2 was identified in the mammary cell lines in culture. In MCF- 10A, this compartment behaved as in MDCK cells; namely it was observed only when the cells cannot form cell-cell contacts. However, in the c arcinoma cell lines MCF-7 and T47D, a significant AP2 intracellular co mpartment was observed also under conditions permissive for the format ion of intercellular contacts. These results were confirmed by immunof luorescence and immunoelectron microscopy experiments that showed VACs in MCF-7 and T47D, even in cells with extensive intercellular contact s. In MCF-7 cells, the addition of serum caused a partial decrease of the AP2 intracellular compartment. The exocytosis of VACs occurred tow ards the center of multi-cellular groups, forming intercellular lumens , similar to those transiently observed in MDCK cells and to structure s described by others during embryo development. Altogether, these res ults suggest that VAC exocytosis is controlled by cell-cell contact si gnalling, which may be defective in carcinoma cells.