Biomedical subjects

Wuhan Xiao

Publications and source records attributed to Wuhan Xiao.

4 recordsLinked to original sources

PubMed2007

Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain.

BACKGROUND: U19/Eaf2 is an androgen-response gene and its downregulation is frequently observed in advanced human prostate cancer. U19/Eaf2 interacts with ELL, a fusion partner of MLL in the (11;19) (q23;p13.1) translocation in acute myeloid leukemia. U19/Eaf2 overexpression induces apoptosis and suppresses xenograft tumor growth. METHODS: Transfection and colony formation were used to assay for apoptosis and growth suppression of various U19/Eaf2 mutants. Co-immunoprecipitation was performed to test the interaction between the U19/Eaf2 constructs and ELL. RESULTS: The region of U19/Eaf2 essential for apoptosis and growth suppression was mapped to amino acids 68-113. This region was necessary and sufficient for binding ELL. Co-expression of U19/Eaf2 and ELL in 293 cells lead to significant increase in cell death and growth suppression. CONCLUSIONS: These observations argue that the interaction with ELL is essential for the induction of apoptosis and growth suppression by U19/Eaf2.

Apoptosis↗

PubMed2006

ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation.

BACKGROUND: U19/Eaf2, an androgen-response gene, is downregulated in advanced human prostate cancer specimens and its overexpression can markedly induce apoptosis in prostate cancer cells. Eleven-nineteen Lysine-rich Leukemia (ELL) is an RNA polymerase II transcription elongation factor, initially identified as a fusion partner gene of MLL in the t(11; 19) (q23; p13.1) chromosomal translocation in acute myeloid leukemia. U19/Eaf2 was previously reported as an ELL-associated factor, a potential transcription factor binds to ELL, forming nuclear speckles in vivo. These findings suggest that ELL-U19/Eaf2 interaction is potentially important in prostate cancer progression and/or acute myeloid leukemia. However, the functional significance of U19/Eaf2 interaction with ELL remains unclear. METHODS: Using co-transfection, co-immunoprecipitation, protein stability assay and transactivation assay, we characterized the consequence of ELL binding to U19/Eaf2. RESULTS: We provide further evidence for U19/Eaf2 as a transcription factor and show that ELL binding is required for nuclear speckle formation of human U19/Eaf2, stabilizes U19/Eaf2 and enhances its transactivation activity. CONCLUSIONS: The above observations indicate ELL may be an important factor required for U19/Eaf2 function because U19/Eaf2 nuclear localization and transactivation activity are essential for its function as a transcription factor.

Base Sequence↗

PubMed2003

Suppression of prostate tumor growth by U19, a novel testosterone-regulated apoptosis inducer.

Androgens control prostate homeostasis and regulate androgen response genes. Here, we report the identification and characterization of U19, a novel testosterone-regulated apoptosis inducer with tumor suppressive activity. U19 is an evolutionarily conserved protein expressed in many human tissues, with the most abundant expression in the prostate, bone marrow, kidney, and lymph nodes. Overexpression of U19 in 12 surveyed cell lines induced apoptosis, and new protein synthesis is required for apoptosis induction. Expression of U19 in xenograft prostate tumors markedly induced apoptosis and inhibited tumor growth in vivo. Consistent with its tumor-suppressive role, U19 down-regulation was observed in all of the surveyed prostate cancer cell lines and in 19 of 23 clinical human prostate tumor specimens. Loss of heterozygosity analysis revealed U19 allelic loss in 19 of the 23 specimens. Furthermore, two of the specimens had homozygous U19 deletions, and one specimen had hypermethylated U19 promoter, indicating that U19 can be inactivated genetically or epigenetically. These observations suggest that U19 is growth inhibitory and tumor suppressive and that the disruption of androgen-dependent growth inhibition via U19 down-regulation is commonly associated with prostate cancer progression.

Amino Acid Sequence↗

PubMed2003

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo.

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959+/-0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G(1)/G(0) cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

Adrenomedullin↗