| 摘要 |
Herein disclosed is an alternatively-spliced [AS] variant of MN/CA9 mRNA and its related protein - AS MN/CA IX. Unlike the tumor-associated, full- length [FL] MN/CA9 mRNA and FL MN/CA IX, which in most tissues signify oncogenesis and/or hypoxia, the AS MN/CA9 mRNA is constitutively-expressed under normoxia and is not stimulated by hypoxia, and the AS MN/CA IX is not confined to the cell membrane. Provided herein are diagnostic/ prognostic methods for preneoplastic/neoplastic disease to differentiate between AS and FL MN/CA9 expression, and probes, primers, and antibodies useful in such methods. Also disclosed are methods to treat pre-neoplastic/neoplastic disease involving the MN gene and protein, which methods are based on the ability of AS MN protein (AS MN/CA IX) to interfere with the catalytic activity of FL MN protein (FL MN/CA IX); such methods may also use AS MN protein fragments that have that interference capability. Such methods may comprise increasing the levels of AS MN/CA IX relative to the levels of FL MN/CA IX. Exemplary therapeutic methods may comprise the administration of agents, such as, AS MN/CA IX itself, a vector expressing AS MN/CA9 mRNA, an antisense oligonucleotide that blocks expression of FL MN/CA IX but not that of AS MN/CA IX, a vector expressing such an antisense oligonucleotide, a FL MN/CA9 isoform-specific siRNA, or a vector expressing such FL MN/CA9 isoform-specific siRNA. Further disclosed are methods to identify agents capable of modulating levels of AS MN/CA IX.
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