TY - JOUR
T1 - Dissecting the Akt/mammalian target of rapamycin signaling network
T2 - Emerging results from the head and neck cancer tissue array initiative
AU - Molinolo, Alfredo A.
AU - Hewitt, Stephen M.
AU - Amornphimoltham, Panomwat
AU - Keelawat, Somboon
AU - Rangdaeng, Samraeung
AU - García, Abelardo Meneses
AU - Raimondi, Ana R.
AU - Jufe, Rafael
AU - Itoiz, María
AU - Gao, Yan
AU - Saranath, Dhananjaya
AU - Kaleebi, George S.
AU - Yoo, George H.
AU - Leak, Lee
AU - Myers, Ernest M.
AU - Shintani, Satoru
AU - Wong, David
AU - Massey, H. Davis
AU - Yeudall, William Andrew
AU - Lonardo, Fulvio
AU - Ensley, John
AU - Gutkind, J. Silvio
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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 fromthe 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.
AB - 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 fromthe 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.
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U2 - 10.1158/1078-0432.CCR-07-1041
DO - 10.1158/1078-0432.CCR-07-1041
M3 - Article
C2 - 17785546
AN - SCOPUS:34548820978
SN - 1078-0432
VL - 13
SP - 4964
EP - 4973
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -