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BMC Physiology (1)
International Journal of Cancer. Journal International du Cancer (1)
Bentley, Brooke (2)
Schwartz, Lawrence M. (2)
Bigelow, Carol (1)
Brown, Christine (1)
Godenschwege, Tanja A (1)
Kim, Chul (1)
Mueller, James (1)
Ravi, Saranya (1)
Rice, Marian (1)
Schwartz, Lawrence M (1)
Scully, Steve J. (1)
Shao, Rong (1)
Shao, Shuang (1)
Srivastava, Sapeckshita (1)
Sun, Danhui (1)
Vaine, Michael (1)
Valavanis, Christos (1)
Wang, Zhaohui (1)
Woodard, Craig T (1)
Yan, Wei (1)
Year of Publication
THE NOVEL LUPUS ANTIGEN RELATED PROTEIN ACHERON ENHANCES THE DEVELOPMENT OF HUMAN BREAST CANCER
Scully, Steve J.
International Journal of Cancer. Journal International du Cancer
Acheron (Achn) is a new member of the Lupus Antigen family of RNA binding proteins. Previous studies have shown that Achn controls developmental decisions in neurons and muscle. In the human mammary gland, Achn expression is restricted to ductal myoepithelial cells. Microarray analysis and immunohistochemistry have shown that Achn expression is elevated in some basal-like ductal carcinomas. To study the possible role of Achn in breast cancer, we engineered human MDA-MB-231 cells to stably express enhanced green fluorescent protein-tagged wild-type Achn (AchnWT), as well as Achn lacking either its nuclear localization signal (AchnNLS) or its nuclear export signal (AchnNES). In in vitro assays, AchnWT and AchnNES, but not AchnNLS, enhanced cell proliferation, lamellipodia formation, and invasive activity and drove expression of the elevated expression of the metastasis-associated proteins MMP-9 and VEGF. To determine if Achn could alter the behavior of human breast cancer cells in vivo, Achn-engineered MDA-MB-231 cells were injected into athymic SCID/Beige mice. AchnWT and AchnNES-expressing tumors displayed enhanced angiogenesis and an approximately five-fold increase in tumor size relative to either control cells or those expressing AchnNLS. These data suggest that Achn enhances human breast tumor growth and vascularization, and that this activity is dependent on nuclear localization.
invasion; metastasis; VEGF; MDA-MB-231 cells; xenograft; MMP9
Acheron, a novel member of the Lupus Antigen family, is induced during the programmed cell death of skeletal muscles in the moth Manduca sexta
In order to identify novel genes associated with the initiation of programmed cell death during development, we employed a differential screening protocol to isolate cDNAs that were induced when the intersegmental muscles (ISM) of the moth Manduca sexta become committed to die at the end of metamorphosis. In this report we provide the first description of Acheron (Achn), a novel protein that was isolated in this screen. Acheron contains three Lupus antigen (La) repeats, nuclear localization and export (NLS and NES) signals, and an RNA recognition motif. Achn defines a new subfamily of La proteins that appears to have branched from authentic La protein relatively late in metazoan evolution. Achn is widely expressed in various insect, mouse and human tissues. Consistent with its expression during ISM death, Achn has been shown in separate studies to control muscle differentiation and apoptosis in both mice and zebrafish. These data define Achn as a newly discovered regulatory molecule that presumably mediates a variety of developmental and homeostatic processes in animals.
apoptosis; 20-hydroxyecdysone; development; metamorphosis; gene expression
Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness
Godenschwege, Tanja A
Woodard, Craig T
One of the hallmarks of Alzheimer's disease, and several other degenerative disorders such as Inclusion Body Myositis, is the abnormal accumulation of amyloid precursor protein (APP) and its proteolytic amyloid peptides. To better understand the pathological consequences of inappropriate APP expression on developing tissues, we generated transgenic flies that express wild-type human APP in the skeletal muscles, and then performed anatomical, electrophysiological, and behavioral analysis of the adults.
We observed that neither muscle development nor animal longevity was compromised in these transgenic animals. However, human APP expressing adults developed age-dependent defects in both climbing and flying. We could advance or retard the onset of symptoms by rearing animals in vials with different surface properties, suggesting that human APP expression-mediated behavioral defects are influenced by muscle activity. Muscles from transgenic animals did not display protein aggregates or structural abnormalities at the light or transmission electron microscopic levels. In agreement with genetic studies performed with developing mammalian myoblasts, we observed that co-expression of the ubiquitin E3 ligase Parkin could ameliorate human APP-induced defects.
These data suggest that: 1) ectopic expression of human APP in fruit flies leads to age- and activity-dependent behavioral defects without overt changes to muscle development or structure; 2) environmental influences can greatly alter the phenotypic consequences of human APP toxicity; and 3) genetic modifiers of APP-induced pathology can be identified and analyzed in this model.
amyloid precursor protein (APP); Drosophila; muscle; mitochondria; electron microscopy; apoptosis; Parkin
Results 1-3 (3)
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