Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer.

International Journal of Radiation Oncology, Biology, Physics
Kathleen M Woods IgnatoskiEvan T Keller

Abstract

External beam radiotherapy (RT) is often used in an attempt to cure localized prostate cancer (PCa), but it is only palliative against disseminated disease. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose expression is reduced in approximately 50% of localized PCa tissues and is absent in metastases. Chemotherapeutic agents have been shown to induce tumor apoptosis through induction of RKIP expression. Our goal was to test whether RT similarly induces apoptosis through induction of RKIP expression. The C4-2B PCa cell line was engineered to overexpress or underexpress RKIP. The engineered cells were tested for apoptosis in cell culture and tumor regression in mice after RT. RT induced both RKIP expression and apoptosis of PCa cells. Overexpression of RKIP sensitized PCa cells to radiation-induced apoptosis. In contrast, short-hairpin targeting of RKIP, so that RT could not induce RKIP expression, protected cells from radiation-induced apoptosis. In a murine model, knockdown of RKIP in PCa cells diminished radiation-induced apoptosis. Molecular concept mapping of genes altered on manipulation of RKIP expression revealed an inverse correlation with the concept of genes altered by RT. The data presented in thi...Continue Reading

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Citations

Jun 12, 2012·Cancer Metastasis Reviews·June Escara-WilkeEvan T Keller
Mar 31, 2012·Clinical & Experimental Metastasis·Peter BirnerSebastian F Schoppmann
Sep 21, 2010·Pathology Oncology Research : POR·Apostolos ZaravinosDemetrios A Spandidos
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Feb 10, 2011·Cancer Research·Fahd Al-MullaWalter Kolch
May 12, 2021·ELife·Ali Ekrem YesilkanalMarsha R Rosner

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