Expression and function of the Pgp MDR-1 gene product in LAMA84.

(A) Flow cytometric analysis of Pgp expression in LAMA84-r and LAMA84-s clones. Note that the histogram for the latter overlaps that of cells stained with the isotypic control. (B) Effect of verapamil on the viability of LAMA84-r cells incubated with 1 μmol/L (left panel) or 2 μmol/L (right panel) STI571. (C) Effect of verapamil on the IC₅₀ of LAMA84 cells. Upper panels show Western blots of LAMA84-s, LAMA84-r, and LAMA84-r treated with verapamil for 2 hours, probed with an anti-phosphotyrosine (pTyr) and with anti-Abl (Bcr-Abl band shown) or anti-actin antibodies. Lower panel illustrates the decrease in the IC₅₀ for Bcr-Abl phosphorylation in LAMA84-r cells exposed to verapamil (VP), as calculated by densitometric analysis of the ratio pTyr-Bcr-Abl/Bcr-Abl or pTyr-Bcr-Abl/actin. We have ascertained that verapamil does not modify the IC₅₀ in LAMA84-s cells (data not shown).