An mRNA differential display comparison of mouse JB6 promotionsensitive (P؉) and -resistant (P؊) cells identified a novel gene product that inhibits neoplastic transformation. The JB6 P؉ and P؊ cells are genetic variants that differ in their transformation response to tumor promoters; P؉ cells form anchorage-independent colonies that are tumorigenic, and P؊ cells do not. A differentially displayed fragment, A7-1, was preferentially expressed in P؊ cells at levels >10-fold those in P؉ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs, also known as MA-3 or TIS, and analogous to human H731 and 197͞15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P؊ than in P؉ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P؊ cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (P؉) phenotype. The antisense-transfected cells were reverted to their initial P؊ phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation.

The novel gene H731 (approved name: PDCD4 (programmed cell death 4)) has been isolated as an antigen gene of the monoclonal antibody Pr-28 which recognized a nuclear antigen in proliferating cells. The gene is homologous to the mouse gene (MA-3/Pdcd4/A7-1) which was associated with apoptosis and was shown to suppress tumor promoter-induced neoplastic transformation. A polyclonal antibody against H731-protein derived from an extract of Escherichia coli transformed with an H731 expression plasmid was prepared, and the H731-protein expression in human normal and tumor cells using the antibody was studied. The staining patterns of asynchronous cultures of human normal fibroblasts (MRC-5) were heterogeneous but the antigen was accumulated in the nuclei at the G0 phase. On the contrary, the antigen was overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines. Immunohistological studies revealed that the H731-protein was highly expressed in bladder carcinoma and breast carcinoma tissues compared with the normal tissues so far tested. These results indicated that expression of the H731-protein was up-regulated or induced in the proliferative cells. Immunohistological studies also revealed that the protein was abundantly expressed in the small duct epithelial cells of the normal mammary gland.

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We demonstrate high-power continuous-wave (CW) lasing oscillation of 1.3-µm wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). Single-mode operation with an output power of over 100 mW, a side-mode suppression ratio (SMSR) of over 50 dB, and a narrow single-lobe beam with a divergence angle of below 1.2° are successfully achieved by using a double-lattice photonic crystal structure consisting of high-aspect-ratio deep air holes. The double lattice is designed to enhance both the in-plane optical feedback and the surface radiation effects in the photonic crystal. The coupling coefficients for 180 ∘ , +90 ∘ , and -90 ∘ diffractions are estimated from the measurements of the photonic band structure as κ1D = 417 cm−1, κ2D+ = 135 cm−1, and κ2D− = 65 cm−1, respectively. The stable single-mode, high-beam-quality operation is attributed to these large coupling coefficients introduced by the asymmetric double-lattice structure.