Transgenic mice expressing constitutively active Akt in oral epithelium validate KLFA as a potential biomarker of head and neck squamous cell carcinoma.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia, of poor prognosis and survival, which frequently displays Akt overactivation. Previously, we reported that mice expressing high levels of constitutively Akt activity (myrAkt) in oral epithelia develop lesions and tumors in the oral cavity.


METHODS
Functional genomics of primary keratinocytes from different transgenic mouse lines and immunostaining of mouse and human samples were performed in order to identify and validate putative biomarkers of oral cancer progression.


RESULTS
The expression of KLF4 was found to be increased only in tumor prone samples from mice bearing overactivation of Akt. Such increased expression was confirmed in oral dysplasias and tumors arising in those mice. Tissue microarray analysis of human samples confirmed the association between active Akt and increased KLF4 expression.


CONCLUSIONS
These data support the notion that KLF4 is potentially a reliable marker of HNSCC, and that myrAkt transgenic mice are valuable tools for preclinical research of HNSCC.
Molecular Oncology Unit, Division of Biomedicine, CIEMAT, Madrid, Spain.
Marta
M
Moral
Carmen
C
Segrelles
Ana Belén
AB
Martínez-Cruz
Corina
C
Lorz
Mirentxu
M
Santos
Ramón
R
García-Escudero
Jerry
J
Lu
Agueda
A
Buitrago
Clotilde
C
Costa
Cristina
C
Saiz
José M
JM
Ariza
Marta
M
Dueñas
Jose L
JL
Rodriguez-Peralto
Francisco J
FJ
Martinez-Tello
Maria
M
Rodriguez-Pinilla
Montserrat
M
Sanchez-Cespedes
John
J
Digiovanni
Jesús M
JM
Paramio
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt