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Cancer metastasis remains the most poorly understood process in cancer biology. It involves the degradation of extracellular matrix (ECM) proteins by a series of 'tumour-associated' proteases. Here we report the identification of a novel protease suppressor, NYD-SP8, which is located on human chromosome 19q13.2. NYD-SP8 encodes a 27 kD GPI-anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). Co-immunoprecipitation experiments showed that NYD-SP8 binds to uPA/uPAR complexes and interfere with active uPA production. Overexpression of NYD-SP8 results in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. These data demonstrate an important role of NYD-SP8 in regulating ECM degradation, providing a novel mechanism that modulates urokinase signalling in the suppression of cancer progression.

Aim: To investigate molecular mechanism of testis development and spermatogenesis., Methods: A human testis cDNA microarray was hybridized with probes from human adult testis, embryo testis and human sperm, and the differential expressed clones were sequenced and analyzed. Expression of PIAS-NY gene was analyzed by RT-PCR., Result: A new isoform of PIAS family, named PIAS-NY, was isolated from human testis cDNA library. It was strongly expressed in adult testis and weakly expressed in both embryo testis and human sperm. Analysis of the open reading frame of PIAS-NY indicated that PIAS-NY was a polypeptide of 405 amino acid residues, and the sequence from the 15th amino acid to the end of PIAS-NY protein was the same as the N-terminal amino acids of PIASx-alpha and PIASx-beta protein. PIAS-NY protein contained two conserved putative LXXLL signature motifs and a zinc binding motif. Tissue distribution analysis revealed that PIAS-NY was predominantly expressed in testis, weakly in the pancreas, and almost imperceptibly in the other organs., Conclusion: PIAS-NY may play important role in testis development and/or spermatogenesis.

Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa., Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa were purified and probes were prepared by a reverse transcription reaction with mRNA as the template. The microarray was hybridized with probes of adult and fetal testes and spermatozoa. The nucleic acid sequences of differentially expressed genes were determined and homologies were searched in the databases of GenBank., Results: A novel human testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was 1 069 bp in length. The cDNA sequence of this clone was deposited in the Genbank (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene, HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison of the differential expressions of PKH and PKH-T in testes of different developmental stages indicated that PKH-T was expressed in the adult testis and spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no expression in the testis of Sertoli cell only and partially spermatogenic arrest patients., Conclusion: PKH-T is a gene highly expressed in adult human testis and spermatozoa. It may play an important role in spermatogenesis and could be related to male infertility.

Aim: To clone a new gene related to human spermatogenesis., Methods: cDNA probes of embryo and adult testis were used to hybridize the cDNA microarray of adult testis, and the clones of differential hybridization were sequenced and analyzed., Results: A novel isoform of calpastatin exclusively and highly expressed in human adult testis was found., Conclusion: A novel isoform of calpastatin expresses in human testis and it is related to spermatogenesis.

This article reviews recent advances in apoptosis on the pathway inducing cancer cell to death, including Bcl-2 family pathway, NF-kappa B pathway, P13K/Akt pathway, Rb gene and p53 gene, especially the targets of anticancer drug in these pathways. It could be useful for the anticancer drug design and estimate. Furthermore, those cancer/testis antigen gene products are potential targets for antigen-specific immunotherapy of carcinoma.