ΔNp63α confers tumor cell resistance to cisplatin through the AKT1 transcriptional regulation

Tanusree Sen, Nilkantha Sen, Mariana Brait Rodrigues De Oliveira, Shahnaz Begum, Aditi Chatterjee, Mohammad Hoque, Edward Ratovitski, David Sidransky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1167-1176
Number of pages10
JournalCancer Research
Volume71
Issue number3
DOIs
StatePublished - Feb 1 2011

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Cisplatin
Neoplasms
Head and Neck Neoplasms
Cell Proliferation
Chromatin Immunoprecipitation
Ovarian Neoplasms
Small Interfering RNA
Neck
Gels
Head
Apoptosis
Lung
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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ΔNp63α confers tumor cell resistance to cisplatin through the AKT1 transcriptional regulation. / Sen, Tanusree; Sen, Nilkantha; Brait Rodrigues De Oliveira, Mariana; Begum, Shahnaz; Chatterjee, Aditi; Hoque, Mohammad; Ratovitski, Edward; Sidransky, David.

In: Cancer Research, Vol. 71, No. 3, 01.02.2011, p. 1167-1176.

Research output: Contribution to journalArticle

Sen, Tanusree ; Sen, Nilkantha ; Brait Rodrigues De Oliveira, Mariana ; Begum, Shahnaz ; Chatterjee, Aditi ; Hoque, Mohammad ; Ratovitski, Edward ; Sidransky, David. / ΔNp63α confers tumor cell resistance to cisplatin through the AKT1 transcriptional regulation. In: Cancer Research. 2011 ; Vol. 71, No. 3. pp. 1167-1176.
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