Alice P. Pentland, M.D.

Research Bio

Research in the Pentland Lab addresses the role of prostaglandins in skin carcinogenesis and in cell differentiation. The role of these lipid mediators in the induction of squamous cell carcinoma of the skin is being studied in the context of ultraviolet light injury. Recent work has shown that significant contributions to tumor initiation and promotion may be made by eicosanoids (arachidonic acid and its metabolites). Most importantly, non-steroidal anti-inflammatory drugs (NSAIDs), which are inhibitors of prostaglandin synthesis, have been shown to have anti-tumor properties in humans. Unfortunately, NSAIDs chemoprevention is limited by NSAID side effects. However, new data shows the hormone metabolizing enzyme aldoketoreductase AKR1C3 is also inhibited by most NSAIDs, begging the question whether cyclooxygenase inhibition is actually the key target through which NSAIDs produce their cancer prevention effects. A potential role in cancer for AKR1C3 has been shown in many tumor types. AKR1C3 metabolizes the cyclooxygenase product PGH2 into PGF2alpha, as well as transforming PGD2 into 9alpha11betaPGF2. This activity can shunt prostaglandin metabolism away from pro-differentiation, pro-apoptotic mediators such as PGJ2. AKR1C3 is also the primary enzyme responsible for synthesis of 17Beta-estradiol and testosterone from their respective less active precursors, supporting its role in hormone sensitive tumors. Lastly, AKR1C3 is capable of supporting redox cycling, which can produce mutations that could promote carcinogenesis.