Dissecting the Akt/Mammalian Target of Rapamycin Signaling Network: Emerging Results from the Head and Neck Cancer Tissue Array Initiative

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developin...

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Published in:	Clinical cancer research Vol. 13; no. 17; pp. 4964 - 4973
Main Authors:	MOLINOLO, Alfredo A, HEWITT, Stephen M, SARANATH, Dhananjaya, KALEEBI, George S, YOO, George H, LEAK, Lee, MYERS, Ernest M, SHINTANI, Satoru, WONG, David, MASSEY, H. Davis, YEUDALL, W. Andrew, LONARDO, Fulvio, AMORNPHIMOLTHAM, Panomwat, ENSLEY, John, GUTKIND, J. Silvio, KEELAWAT, Somboon, RANGDAENG, Samraeung, MENESES GARCIA, Abelardo, RAIMONDI, Ana R, JUFE, Rafael, ITOIZ, Maria, YAN GAO
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-09-2007
Subjects:	Akt Antineoplastic agents Biological and medical sciences Carcinoma, Squamous Cell - metabolism Cyclooxygenase 2 - analysis formalin-fixed tissue head and neck cancer Head and Neck Neoplasms - metabolism Humans Immunohistochemistry Mechanistic Target of Rapamycin Complex 1 Medical sciences mTOR Multiprotein Complexes oral cancer Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Pharmacology. Drug treatments Proteins Proto-Oncogene Proteins c-akt - analysis Receptor, Epidermal Growth Factor - analysis Signal Transduction - physiology Tissue Array Analysis - methods tissue-microarray TOR Serine-Threonine Kinases Transcription Factors - analysis Tumor Suppressor Protein p53 - analysis Tumor Suppressor Proteins - analysis Tumors Protein kinase mTOR Signal transduction DNA chip Network Mammalian target of rapamycin Akt protein kinase ENT disease Head and neck cancer Malignant tumor
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Summary:	Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-07-1041