Abstract：
:Strategies to address resistance to platin drugs are greatly needed in human epithelial cancers (e.g., ovarian, head/neck, and lung) where platins are used widely and resistance occurs commonly. We found that upon ΔNp63α overexpression, AKT1 and phospho-AKT1 levels are upregulated in cancer cells. Investigations using gel-shift, chromatin immunoprecipitation and functional reporter assays implicated ΔNp63α in positive regulation of AKT1 transcription. Importantly, we found that ΔNp63α, AKT1, and phospho-AKT levels are greater in 2008CI3 CDDP-resistant ovarian cancer cells than in 2008 CDDP-sensitive cells. siRNA-mediated knockdown of ΔNp63α expression dramatically decreased AKT1 expression, whereas knockdown of either ΔNp63α or AKT1 decreased cell proliferation and increased death of ovarian and head/neck cancer cells. Conversely, enforced expression of ΔNp63α increased cancer cell proliferation and reduced apoptosis. Together, our findings define a novel ΔNp63α-dependent regulatory mechanism for AKT1 expression and its role in chemotherapeutic resistance of ovarian and head/neck cancer cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Sen T,Sen N,Brait M,Begum S,Chatterjee A,Hoque MO,Ratovitski E,Sidransky Ddoi
10.1158/0008-5472.CAN-10-1481subject
Has Abstractpub_date
2011-02-01 00:00:00pages
1167-76issue
3eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-1481journal_volume
71pub_type
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