title: Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4330, USA.
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Panomwat
authors.initials: P
authors.lastname: Amornphimoltham
authors.forename: Somboon
authors.initials: S
authors.lastname: Keelawat
authors.forename: Samraeung
authors.initials: S
authors.lastname: Rangdaeng
authors.forename: Abelardo
authors.initials: A
authors.lastname: Meneses García
authors.forename: Ana R
authors.initials: AR
authors.lastname: Raimondi
authors.forename: Rafael
authors.initials: R
authors.lastname: Jufe
authors.forename: María
authors.initials: M
authors.lastname: Itoiz
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Dhananjaya
authors.initials: D
authors.lastname: Saranath
authors.forename: George S
authors.initials: GS
authors.lastname: Kaleebi
authors.forename: George H
authors.initials: GH
authors.lastname: Yoo
authors.forename: Lee
authors.initials: L
authors.lastname: Leak
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Myers
authors.forename: Satoru
authors.initials: S
authors.lastname: Shintani
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.forename: H Davis
authors.initials: HD
authors.lastname: Massey
authors.forename: W Andrew
authors.initials: WA
authors.lastname: Yeudall
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: John
authors.initials: J
authors.lastname: Ensley
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D046888:Tissue Array Analysis / Q000379:methods*; D014157:Transcription Factors / Q000032:analysis*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis