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A regulator of the protein phosphatase 2A (PP2A), a4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of a4 in human cell transformation and tumorigenesis, we show that a4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B 1 , N-methyl-N 0 -nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of a4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that a4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated a4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of a4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed a4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of a4 through specific binding to the 3 0 -untranslated region of a4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that a4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced a4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.

The temperature- and bias-dependent photocurrent spectra of very long wavelength GaAs/AlGaAs quantum well infrared photodetectors (QWIPs) are studied using spectroscopic measurements and corresponding theoretical calculations. It is found that the peak response wavelength will shift as the bias and temperature change. Aided by band structure calculations, we propose a model of the double excited states and explain the experimental observations very well. In addition, the working mechanisms of the quasi-bound state confined in the quantum well, including the processes of tunneling and thermionic emission, are also investigated in detail. We confirm that the first excited state, which belongs to the quasi-bound state, can be converted into a quasi-continuum state induced by bias and temperature. These obtained results provide a full understanding of the bound-to-quasi-bound state and the bound-to-quasi-continuum state transition, and thus allow for a better optimization of QWIPs performance.

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