Functional Protein Pathway Activation Mapping of the Progression of Normal Skin to Squamous Cell Carcinoma
| Autor: | G. Timothy Bowden, Caterina Longo, Robert S. Krouse, Emanuel F. Petricoin, Jianghong Deng, David S. Alberts, Janine G. Einspahr, Valerie S. Calvert, Steven P. Stratton, Anil Prasad, Lance A. Liotta, Giovanni Pellicani, Yira Bermudez, Clara Curiel-Lewandrowski, James Warneke, Paul Sagerman |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male MAPK/ERK pathway Cancer Research Cell signaling Skin Neoplasms Adolescent Upstream and downstream (transduction) Laser Capture Microdissection Article Young Adult 80 and over Humans Prospective Studies Epidermal growth factor receptor Phosphorylation PI3K/AKT/mTOR pathway Aged Skin Laser capture microdissection Aged 80 and over biology Carcinoma Squamous Cell Disease Progression Female Middle Aged Prognosis Signal Transduction Carcinoma Squamous Cell stomatognathic diseases Oncology Immunology Cancer research biology.protein Signal transduction |
| Zdroj: | Cancer Prevention Research. 5:403-413 |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK–ERK [mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK–ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation–driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications. Cancer Prev Res; 5(3); 403–13. ©2012 AACR. |
| Databáze: | OpenAIRE |
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