BACKGROUND: The enzyme mammalian target of rapamycin (mTOR) integrates many different cellular signals to control cell growth and proliferation, protein synthesis and breakdown, and other processes. Dysregulation of mTOR is implicated in a range of human diseases, including cancers and cardiovascular disorders. To date, there has been no report on the expression of protein kinase B (AKT)/mTOR cell signalling in epidermal tumours. OBJECTIVES: This study was designed to investigate the activation of the mTOR signalling pathway in epidermal tumours and to correlate this with cyclin-dependent kinase 2 (CDK2) expression. METHODS: Immunohistological staining was performed with phosphorylated (p-) AKT, p-mTOR, p-4E-binding protein 1 (p-4EBP1), p-ribosomal protein S6 (p-S6), p-p70 ribosomal protein S6 kinase 1 (p-p70S6K1) and CDK2 in 15 cases each of seborrhoeic keratosis, actinic keratosis, keratoacanthoma and Bowen's disease (BD), and 25 cases of squamous cell carcinoma (SCC). Fifteen normal skin (NS) samples served as control. RESULTS: Among 85 tumours, 40 (47%) were positive for p-AKT, 31 (36%) for p-mTOR, 44 (52%) for p-4EBP1, 38 (45%) for p-S6, and 39 (46%) for p-p70S6K1. CDK2 immunostaining was positive in all cases of SCC and BD, and in 67% of benign tumours. All of these markers were stained much more frequently in malignant tumours than in benign tumours or NS. p-AKT, p-mTOR, p-4EBP1, p-p70S6K1 and p-S6 each showed high correlation with CDK2. CONCLUSIONS: Constitutive activation of the AKT/mTOR pathway was frequent in epidermal tumours, especially in malignant tumours. Activation was highly correlated with CDK2 expression, suggesting that the AKT/mTOR pathway may induce the malignant transition through CDK2 in epidermal tumours.
BACKGROUND: The enzyme mammalian target of rapamycin (mTOR) integrates many different cellular signals to control cell growth and proliferation, protein synthesis and breakdown, and other processes. Dysregulation of mTOR is implicated in a range of human diseases, including cancers and cardiovascular disorders. To date, there has been no report on the expression of protein kinase B (AKT)/mTOR cell signalling in epidermal tumours. OBJECTIVES: This study was designed to investigate the activation of the mTOR signalling pathway in epidermal tumours and to correlate this with cyclin-dependent kinase 2 (CDK2) expression. METHODS: Immunohistological staining was performed with phosphorylated (p-) AKT, p-mTOR, p-4E-binding protein 1 (p-4EBP1), p-ribosomal protein S6 (p-S6), p-p70 ribosomal protein S6 kinase 1 (p-p70S6K1) and CDK2 in 15 cases each of seborrhoeic keratosis, actinic keratosis, keratoacanthoma and Bowen's disease (BD), and 25 cases of squamous cell carcinoma (SCC). Fifteen normal skin (NS) samples served as control. RESULTS: Among 85 tumours, 40 (47%) were positive for p-AKT, 31 (36%) for p-mTOR, 44 (52%) for p-4EBP1, 38 (45%) for p-S6, and 39 (46%) for p-p70S6K1. CDK2 immunostaining was positive in all cases of SCC and BD, and in 67% of benign tumours. All of these markers were stained much more frequently in malignant tumours than in benign tumours or NS. p-AKT, p-mTOR, p-4EBP1, p-p70S6K1 and p-S6 each showed high correlation with CDK2. CONCLUSIONS: Constitutive activation of the AKT/mTOR pathway was frequent in epidermal tumours, especially in malignant tumours. Activation was highly correlated with CDK2 expression, suggesting that the AKT/mTOR pathway may induce the malignant transition through CDK2 in epidermal tumours.
Authors: Jean Christopher Chamcheu; Vaqar M Adhami; Stephane Esnault; Mario Sechi; Imtiaz A Siddiqui; Kenneth A Satyshur; Deeba N Syed; Shah-Jahan M Dodwad; Maria-Ines Chaves-Rodriquez; B Jack Longley; Gary S Wood; Hasan Mukhtar Journal: Antioxid Redox Signal Date: 2016-10-04 Impact factor: 8.401
Authors: Yira Bermudez; Steven P Stratton; Clara Curiel-Lewandrowski; James Warneke; Chengcheng Hu; George T Bowden; Sally E Dickinson; Zigang Dong; Ann M Bode; Kathylynn Saboda; Christine A Brooks; Emanuel F Petricoin; Craig A Hurst; David S Alberts; Janine G Einspahr Journal: Cancer Prev Res (Phila) Date: 2015-06-01
Authors: Janine G Einspahr; Valerie Calvert; David S Alberts; Clara Curiel-Lewandrowski; James Warneke; Robert Krouse; Steven P Stratton; Lance Liotta; Caterina Longo; Giovanni Pellacani; Giovanni Pellicani; Anil Prasad; Paul Sagerman; Yira Bermudez; Jianghong Deng; G Timothy Bowden; Emanuel F Petricoin Journal: Cancer Prev Res (Phila) Date: 2012-03
Authors: Sally E Dickinson; Jaroslav Janda; Jane Criswell; Karen Blohm-Mangone; Erik R Olson; Zhonglin Liu; Christy Barber; Emanuel F Petricoin; Valerie S Calvert; Janine Einspahr; Jesse E Dickinson; Steven P Stratton; Clara Curiel-Lewandrowski; Kathylynn Saboda; Chengcheng Hu; Ann M Bode; Zigang Dong; David S Alberts; G Timothy Bowden Journal: Cancer Prev Res (Phila) Date: 2016-01-22