ROLE OF THE MICROTUBULAR SYSTEM IN MORPHOLOGICAL ORGANIZATION OF NORMAL AND ONCOGENE-TRANSFECTED EPITHELIAL-CELLS

To understand better the role of the microtubular system in the develo pment and maintenance of morphological organization of nonpolarized an d polarized cells of the same origin we examined the effects of two mi crotubule-specific drugs, colcemid and taxol, on discoid cultured epit helial rat cells of the IAR-2 line and on polarized cells obtained fro m this line by transfection of mutated N-ras oncogene; morphometric, i mmunomorphologic, and videomicroscopic methods were used. Depolymeriza tion of microtubules by colcemid did not cause major changes in the di scoid shape of IAR cells but altered organization of actin cortex; in particular, it led to disappearance of circumferential bundle of actin microfilaments. Taxol reorganized the normal network of microtubules radiating from the perinuclear centers into numerous arrays of short m icrotubules not associated with any centers. Taxol-treated cells had w ider circumferential bundles of microfilaments than control cells and morphometric analysis showed that their contours were closer to geomet ric circle than those of control or of colcemid-treated cells. These d ata show that function of the microtubular system is essential for mai ntenance of the characteristic morphological organization of discoid c ells; we propose to name this function ''contra-polarization.'' Contra -polarization is not prevented and is even promoted by taxol; this res ult suggests that a decentralized system of microtubules is sufficient for this function. In contrast, maintenance of polarized morphology o f IAR-2 cells transfected by the N-ras oncogene is inhibited not only by colcemid but also by taxol and thus requires the presence of a norm al centralized microtubular system.