Ping-Chang Kuo

Breast Cancer Amplified Sequence 2, a Novel Negative Regulator of the p53 Tumor Suppressor

Breast cancer amplified sequence 2 (BCAS2) was reported previously as a transcriptional coactivator of estrogen receptor. Here, we report that BCAS2 directly interacts with p53 to reduce p53 transcriptional activity by mildly but consistently decreasing p53 protein in the absence of DNA damage. However, in the presence of DNA damage, BCAS2 prominently reduces p53 protein and provides protection against chemotherapeutic agent such as doxorubicin. Deprivation of BCAS2 induces apoptosis in p53 wild-type cells but causes G(2)-M arrest in p53-null or p53 mutant cells. There are at least two apoptosis mechanisms induced by silencing BCAS2 in wild-type p53-containing cells. Firstly, it increases p53 retention in nucleus that triggers the expression of apoptosis-related genes. Secondly, it increases p53 transcriptional activity by raising p53 phosphorylation at Ser(46) and decreases p53 protein degradation by reducing p53 phosphorylation at Ser(315). We show for the first time that BCAS2, a small nuclear protein (26 kDa), is a novel negative regulator of p53 and hence a potential molecular target for cancer therapy.

Viral delivery of heme oxygenase-1 attenuates photoreceptor apoptosis in an experimental model of retinal detachment

This study was designed to evaluate the efficacy of subretinal injection of recombinant adeno-associated virus vector expressing heme oxygenase-1 (rAAV-HO-1) in attenuating photoreceptor apoptosis induced by experimental retinal detachment (RD) in Sprague-Dawley rats. Our results disclosed that subretinal rAAV-HO-1 delivery achieved localized high HO-1 gene expression in retinal outer nuclear layer (ONL) compared with rAAV-lacZ-injected eyes and eyes with RD left untreated both at 2 (p=0.003) and 28 (p=0.007) days of RD. The ONL thickness (p=0.018) and mean photoreceptor nuclei count (p=0.009) in eyes receiving rAAV-HO-1 injection was significantly higher than in rAAV-lacZ-injected or eyes with RD left untreated at 28 days of RD. There were fewer apoptotic photoreceptor nuclei at 2 (p=0.008) and 5 (p=0.018) days of RD and less activated caspase-3 expression (p=0.008) at 2 days of RD in rAAV-HO-1 treated eyes than in control eyes. These data supported that gene transfer approach might attenuate photoreceptor apoptosis caused by RD with a resultant better ONL preservation.

BCAS2 is essential for Drosophila viability and functions in pre-mRNA splicing

Here, we show that dBCAS2 (CG4980, human Breast Carcinoma Amplified Sequence 2 ortholog) is essential for the viability of Drosophila melanogaster. We find that ubiquitous or tissue-specific depletion of dBCAS2 leads to larval lethality, wing deformities, impaired splicing, and apoptosis. More importantly, overexpression of hBCAS2 rescues these defects. Furthermore, the C-terminal coiled-coil domain of hBCAS2 binds directly to CDC5L and recruits hPrp19/PLRG1 to form a core complex for splicing in mammalian cells and can partially restore wing damage induced by knocking down dBCAS2 in flies. In summary, Drosophila and human BCAS2 share a similar function in RNA splicing, which affects cell viability.

BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability

Background:We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR.Methods:Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively.Results:BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome.Conclusions:In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.

Microstructure and Magnetic Performance of Perpendicularly Magnetic Anisotropic Fe

L1₀-FePt(001) films with compositional gradient was proposed to realize the graded film with magnetic perpendicular anisotropy in this study. A hard magnetic layer of 5 nm-thick stoichiometry L1₀ FePt was initially deposited onto a glass substrate with a thin MgO underlayer. The hard layer exhibits strong (001) texture, island-type surface morphology, high perpendicular magnetic anisotropy (PMA), and large out-of-plane coercivity (H_c⊥) of about 20 kOe at room temperature (RT). A 5-nm-thick compositionally graded Fe-Pt layer was then deposited on the L1₀ FePt hard layer at deposition temperatures (T_d) from 300 to 450°C. Good (001)-texture is retained in the graded layer and the island-type morphology is preserved when T_d ≤ 400°C. A significant reduction in H_c⊥ from 20 to around 7 kOe was achieved. Besides, the graded films exhibit magnetically single-phase reversal behavior with a high anisotropy field (H₀) of ~90 kOe. When T_d > 400°C, PMA of the films was reduced due to the extensive diffusion between the Fe-rich graded and hard layers. Our proposed scheme demonstrate the feasibility of magnetic gradation induced by binary composition variation in FePt films, providing useful information for designing future ultrahigh magnetic recording media.

_{3}

The FePt(30 nm)/MgO bilayer films with various MgO(200) underlayer thicknesses of 0 to 30 nm are in-situ deposited on Si substrates. A weak (111)FePt peak as well as strong (001)FePt and (002)FePt peaks are observed in XRD pattern of single-layered FePt film with no MgO underlayer. When a 5 nm thick MgO film is introduced under the FePt film, the (111)FePt peak almost disappears and both the (001)FePt and (002)FePt peaks are enhanced greatly. This indicates that the perpendicular magnetic anisotropy of FePt film can be improved by introduction of a thinner MgO underlayer. However, a weak (111)FePt peak appears again as the MgO underlayer is increased to 10 nm, revealing that the perpendicular magnetic anisotropy of FePt film will be deteriorated by introducing a thicker MgO underlayer.

Pt/Fe

FePt thin films with different thicknesses (2.5-30 nm) were deposited alternately with Fe and Pt layers on amorphous SiO₂ substrate without any underlayer and then were postannealed at 700°C for 30 min. The dependences of microstructures, degree of ordering, and magnetic properties on FePt film thickness were investigated. The fct-FePt (001) texture films could be obtained by dc magnetron sputtering of (Fe/Pt)_n multilayer on amorphous SiO₂ substrate after annealing at 700°C for 30 min. The increasing degree of L1₀ ordering was probably due to the thicker films providing more L1₀-ordering nucleation sites. The island-like FePt grains formed on the SiO₂ substrates as the film was thinner than 7.5 nm. Both the values of out-of-plane squareness (S_⊥) and coercivity (Hc_⊥) were higher than those of in-plane ones for all film thicknesses. The values of S_⊥ are close to 1 and Hc_⊥ are in the range of 9.0-15 kOe for FePt thin films with a thickness of 5-15 nm after annealing at 700°C for 30 min.

_{2}

Abstract The highly textured Nd0.6Sr0.4MnO3 thin films with different thickness t were obtained. The maximum magnetoresistance (MR) ratio, defined as [R(0)−R(1.5 T )]/R(0) at the insulating- to metallic-phase transition temperature, was found to increase with decreasing t, reaching a value of 75% for t=500 A. However, when t was further decreased down to 100 A, the MR ratio was not significantly affected. In conjunction with our topographic results, we have attributed the saturation of MR ratio to the achieving of an optimized interface strain.

Pt/

Ta/Si bilayer thin films were prepared by magnetron sputtering. The recording mechanism and dynamic tests for write-once blu-ray disc (BD-R) are investigated. Thermal analysis shows that the Ta/Si bilayer thin film has a reflectivity change with the temperature ranging from 130 °C to 300 °C. It was found that the as-deposited phase of Ta/Si bilayer film was Ta phase and it would transform to Ta and TaSi2 coexisting phases after annealing at 350 °C for 30 min. Dynamic tests show that the Ta/Si bilayer thin films are suitable for BD-R.

L1_{0}

GeCu(6 nm)/Si(6 nm) bilayer recording thin film was prepared by magnetron sputtering on nature oxidized silicon wafer and polycarbonate substrate by magnetron sputtering. The thermal property, crystallization mechanism, and recording characteristics of the GeCu/Si bilayer thin film were investigated. Thermal analysis shows that the GeCu/Si bilayer thin film has two reflectivity changes with the temperature ranges, 120 °C ∼ 165 °C and 310 °C∼ 340 °C. Dynamic tests show that the optimum jitter values at recording speeds of 1X, 2X, 4X, and 5X are 5.8%, 6%, 5.9%, and 6%, respectively. It indicates that GeCu/Si bilayer film is potentially useful in write-once blu-ray optical disc.