KLF4 expression and aberrant transforming growth factor beta pathway in head and neck cancer.

ALVAREZ RS; SANCHEZ V; BAL DE KIER JOFF¨¦ E; GUTKIND JS; RAIMONDI AR

Cordoba

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010

SISTAM

KLF4 expression and aberrant transforming growth factor b pathway in head and neck cancer. Alvarez RS, Sanchez V, Bal de Kier Joff¨¦ E, Gutkind JS1, Raimondi AR. Institute of Oncology Angel H. Roffo, University of Buenos Aires, Argentina. 1Oral and Pharyngeal Cancer Branch, NIDCR, NIH, USA. Head and neck cancer (HNC) is among the six most prevalent cancers in the world. Despite improvements in treatment, survival has not changed over the past 30 years. KLF4 is a transcription factor associated with carcinogenesis and tumor suppression. KLF4 is expressed in differentiated cells of normal stratified epithelia. Here we analyze the expression of KLF4 in HNC and its possible association with TGFb pathway. We studied the basal expression levels of KLF4 in HNC cells by western blot. Increased level of KLF4 was detected in all cell lines compared with normal keratinocytes. After treatment of HNC lines with TGF¦Â1 we found reduced expression of KLF4 in HN13 cells. When we studied the viability of cells by MTS assays, none of the HNC cells showed growth inhibition by TGF¦Â1; however HN30 presented a partial reduction of 10%. To further understand TGFb resistance we studied the induction of pSmad2 and p21. HNC cells showed induction of pSmad2; no change was found in HN12 cells for p21. Overall, HNC cells presented a significant resistance to TGF¦Â growth inhibitory effect. HNC cells retained smad2 activation and HN13 a regulation in KLF4 expression. The progressive disruption of TGFb signaling and the changes in KLF4 regulation may reflect different stages in oral tumorigenesis.