PTEN as a unique promising therapeutic target for occupational asthma.
The tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN) dephophorylates phosphatidylinositol 3,4,5-triphosphate (PIP3) and is a key negative regulator of phosphoinositide kinase-3 (PI3K) signaling pathway. PTEN also suppresses cellular motility through mechanisms that may be partially independent of phosphatase activity. PTEN is one of the most commonly lost tumor suppressors in human cancers, and its down-regulation is also implicated in several other diseases including airway inflammatory diseases. There is increasing evidence regarding the protective effects of PTEN on the bronchial asthma which is induced by complex signaling networks. Very recently, as for the occupational asthma (OA) with considerable controversy for its pathobiologic mechanisms, PTEN has been considered as a key molecule which is capable of protecting toluene diisocyanate (TDI)-induced asthma, suggesting that PTEN is located at switching point of various molecular signals in OA. Knowledge of the mechanisms of PTEN regulation/function could direct to the pharmacological manipulation of PTEN. This article reviews the latest knowledge and studies on the roles and mechanisms of PTEN in OA.
Kim
So Ri
SR
Department of Internal Medicine, Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju, South Korea.
Lee
Yong Chul
YC
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D006801:Humans; D009784:Occupational Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects / Q000633:toxicity
D018927:Anti-Asthmatic Agents; D014051:Toluene 2,4-Diisocyanate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human