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2 Publications

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    Magee Lab
    06/15/02 | Phosphorylation-dependent differences in the activation properties of distal and proximal dendritic Na+ channels in rat CA1 hippocampal neurons.
    Gasparini S, Magee JC
    The Journal of Physiology. 2002 Jun 15;541(Pt 3):665-72. doi: 10.1002/cbic.201000254

    {At distal dendritic locations, the threshold for action potential generation is higher and the amplitude of back-propagating spikes is decreased. To study whether these characteristics depend upon Na+ channels, their voltage-dependent properties at proximal and distal dendritic locations were compared in CA1 hippocampal neurons. Distal Na+ channels activated at more hyperpolarized voltages than proximal (half-activation voltages were -20.4 +/- 2.4 mV vs. -12.0 +/- 1.7 mV for distal and proximal patches, respectively

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    Magee Lab
    03/01/02 | Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia.
    Abdulkadir SA, Magee JA, Peters TJ, Kaleem Z, Naughton CK, Humphrey PA, Milbrandt J
    Molecular and Cellular Biology. 2002 Mar;22(5):1495-503. doi: 10.1002/cbic.201000254

    The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein expression is common in human prostate carcinomas and prostatic intraepithelial neoplasia (PIN) lesions and correlates with tumor progression. Disruption of the murine Nkx3.1 gene results in defects in prostate branching morphogenesis, secretions, and growth. To more closely mimic the pattern of NKX3.1 loss that occurs in human prostate tumors, we have used Cre- and loxP-mediated recombination to delete the Nkx3.1 gene in the prostates of adult transgenic mice. Conditional deletion of one or both alleles of Nkx3.1 leads to the development of preinvasive lesions that resemble PIN. The pattern of expression of several biomarkers (Ki-67, E-cadherin, and high-molecular-weight cytokeratins) in these PIN lesions resembled that observed in human cases of PIN. Furthermore, PIN foci in mice with conditional deletion of a single Nkx3.1 allele lose expression of the wild-type allele. Our results support the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this gene in tumor initiation.

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