Isolation and characterization of a novel human bladder cancer cell line: BK10

Summary Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content 〈4n〉 with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful too for the further study of bladder carcinoma oncogenesis and gene therapy.     

The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3

Mucins provide a protective barrier for epithelial surfaces, and their overexpression in tumors has been implicated in malignancy. We have previously demonstrated that Muc4, a transmembrane mucin that promotes tumor growth and metastasis, physically interacts with the ErbB2 receptor tyrosine kinase and augments receptor tyrosine phosphorylation in response to the neuregulin-1beta (NRG1beta) growth factor. In the present study we demonstrate that Muc4 expression in A375 human melanoma cells, as well as MCF7 and T47D human breast cancer cells, enhances NRG1beta signaling through the phosphatidylinositol 3-kinase pathway. In examining the mechanism underlying Muc4-potentiated ErbB2 signaling, we found that Muc4 expression markedly augments NRG1beta binding to A375 cells without altering the total quantity of receptors expressed by the cells. Cell-surface protein biotinylation experiments and immunofluorescence studies suggest that Muc4 induces the relocalization of the ErbB2 and ErbB3 receptors from intracellular compartments to the plasma membrane. Moreover, Muc4 interferes with the accumulation of surface receptors within internal compartments following NRG1beta treatment by suppressing the efficiency of receptor internalization. These observations suggest that transmembrane mucins can modulate receptor tyrosine kinase signaling by influencing receptor localization and trafficking and contribute to our understanding of the mechanisms by which mucins contribute to tumor growth and progression.     

The spatial structures of hypolithic communities in the Dry Valleys of East Antarctica

Hypolithic communities represent important reservoirs of microbial life in hyper-arid deserts. A number of studies on the diversity and ecology of these communities from different geographic areas have been reported in the past decade, but the spatial distribution of the different components of these communities is still not understood. Moss- and cyanobacteria-dominated hypolithic community morphotypes from Miers Valley (McMurdo Dry Valleys, East Antarctica) were analyzed by electron microscopy in order to characterize the microscale spatial structure. The two communities showed a high degree of internal organization, but differing according to the biological composition. In moss-dominated hypoliths, the moss plantlets are intermixed with mineral fragments of soil origin. However, in cyanobacteria-dominated hypoliths, a layered spatial organization was structured by filamentous cyanobacteria and associated extracellular polymeric components. While moss cells were lacking in cyanobacteria-dominated communities, biofilms formed by cyanobacteria and heterotrophic bacteria were observed in both community morphotypes. The water-holding capacity of both live and dead moss cells and the associated organic matrix, together with the protective properties of the extracellular polymeric substances, could facilitate the survival and activity of these communities. Similar structural strategies can favor the survival of microbial communities in different extreme environments.     

The phylogeography of Adelie penguin faecal flora

The gut of animals changes quickly from a totally sterile environment before birth to a numerous and highly diverse microbial community shortly after birth. However, few studies have examined the source of the bacteria colonizing the gut. We used a genetic based approach to investigate the distribution and acquisition of faecal microbial communities by Adelie penguins, Pygoscelis adeliae , breeding in the Ross Sea region of Antarctica by cloning a portion of the 16S rRNA gene and by automated ribosomal intergenic spacer analysis (ARISA). We hypothesized that bacteria were either acquired from the penguins' neighbours or inherited from their ancestors. Samples were collected from Adelie penguin breeding colonies at the north-western edge of the Ross Sea coast through to the southernmost Adelie penguin colonies on Ross Island. Most of the bacterial sequences we obtained were only distantly homologous with previously published sequences. Bacterial taxa appear to have a restricted distribution as the majority of 16S rRNA clones were isolated from only one or two hosts. Faecal bacterial community similarity was strongly negatively correlated with the genetic distance between hosts suggesting that bacterial communities are inherited. There was little support for a correlation between distance between collection sites and community similarity.     

Neuregulin-1 enhances depolarization-induced GABA release

Neuregulin-1 (NRG1), a regulator of neural development, has been shown to regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1 receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons, little is known about its role in GABAergic transmission. We show that ErbB4 is localized at GABAergic terminals of the prefrontal cortex. Our data indicate a role of NRG1, both endogenous and exogenous, in regulation of GABAergic transmission. This effect was blocked by inhibition or mutation of ErbB4, suggesting the involvement of ErbB4. Together, these results indicate that NRG1 regulates GABAergic transmission via presynaptic ErbB4 receptors, identifying a novel function of NRG1. Because both NRG1 and ErbB4 have emerged as susceptibility genes of schizophrenia, these observations may suggest a mechanism for abnormal GABAergic neurotransmission in this disorder.     

Neuronal migration in the adult brain: are we there yet?

The generation and targeting of appropriate numbers and types of neurons to where they are needed in the brain is essential for the establishment, maintenance and modification of neural circuitry. This review aims to summarize the patterns, mechanisms and functional significance of neuronal migration in the postnatal brain, with an emphasis on the migratory events that persist in the mature brain.     

Pathway information for systems biology

Pathway information is vital for successful quantitative modeling of biological systems. The almost 170 online pathway databases vary widely in coverage and representation of biological processes, making their use extremely difficult. Future pathway information systems for querying, visualization and analysis must support standard exchange formats to successfully integrate data on a large scale. Such integrated systems will greatly facilitate the constructive cycle of computational model building and experimental verification that lies at the heart of systems biology.