Re-expression of LKB1 in LKB1-mutant EKVX cells leads to resistance to paclitaxel through the up-regulation of MDR1 expression.

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Kaisheng MaoWei Zhou

Abstract

The tumor suppressor LKB1 has recently been shown to be involved in the regulation of microtubule dynamics, thus cancer cells with inactivated LKB1 may have developed a means to overcome dysregulated microtubule functions, making them intrinsically resistant to microtubule targeting agents. Here, we generated isogenic LKB1-wild type and mutant non-small cell lung cancer (NSCLC) cell lines to evaluate the role of LKB1 in paclitaxel resistance. SRB, flow cytometry and immunoblotting were used to assess cell proliferation and apoptosis in NSCLC cell lines after paclitaxel treatment. Expression of LKB1 was restored in LKB1-null cells by retrovirus infection and was reduced in LKB1-wild type cells by shRNA knock down. The restoration of LKB1 in LKB1-null cells failed to promote paclitaxel-induced apoptosis in both p53-wild type and p53-mutant backgrounds, indicating that LKB1 was not required for paclitaxel-induced apoptosis. Interestingly, the re-establishment of LKB1 expression led to the up-regulation of class III beta-tubulin and MDR1 in EKVX cells. The up-regulation of MDR1 protein and transcripts in EKVX cells was specifically associated with the expression of wild-type LKB1 and mainly responsible for the increased cellular re...Continue Reading

References

Feb 12, 2005·Science·Masashi KishiJoshua R Sanes
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Feb 16, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jean-Louis PujolJean-Pierre Daurès
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Jul 11, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Diansheng ZhongWei Zhou
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Sep 5, 2013·JAMA : the Journal of the American Medical Association

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