Suppression of P‐glycoprotein gene expression in Hs578T/Dox by the overexpression of caveolin‐1

Publisher Website
Google Scholar
Abstract
Caveolin‐1, the principal component of caveolae, is a 21–24 kDa integral membrane protein. The interaction of the caveolin‐1 scaffolding domain with signaling molecules can functionally inhibit the activity of these signaling proteins. Little is known about how caveolin‐1 influences the expression of P‐glycoprotein (P‐gp), an ABC transporter encoded by multi‐drug resistance (MDR1) gene. To elucidate the possible mechanism between caveolin‐1 and P‐gp expression, in the present study, we overexpressed caveolin‐1 in the Hs578T/Dox breast adenocarcinoma cells, a multidrug resistant line, and then selected single clone cells highly expressing caveolin‐1 level. Both Western blot and confocal microscopy analyses showed that caveolin‐1 was markedly overexpressed in the transfectants, while P‐gp protein was almost abolished. Reverse transcription polymerase chain reaction also showed that the expression of P‐gp mRNA was significantly suppressed in the transfectants. It was confirmed further by Northern blot analysis. Moreover, through measuring the changes of drug resistance and P‐gp transport activity in the transfectants, we found that overexpression of caveolin‐1 reversed drug resistance of transfectants and lowered their P‐gp transport activity to the level of Hs578T/S. Taken together, our results indicate that such suppression of P‐gp in the transfectants overexpressing caveolin‐1 may occur at the transcriptional level.