Expression analysis of TEM8 and CMG2 in normal and patient-specific prostate cancer




Vargas, Micaela

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Tumor endothelial marker 8 (TEM8) and capillary morphogenesis gene 2 (CMG2), both single-pass integral membrane proteins, are suggested players in angiogenesis. They also serve as anthrax toxin receptors. The focus of this work has been to analyze the expression of all splice variants of both genes in a large number of normal human tissues, as well as patient-specific prostate cancer tissues. Semi-quantitative nested PCR was used for this analysis. TEM8 V1 and V2 are membrane-bound, V3 is secreted. CMG2 386, 488, and 489 are membrane-bound, 322 is secreted. Analysis of nearly 30 normal tissues shows that TEM8 V3 transcript is ubiquitous, while V2 expression is tissue-specific and developmental. The work also identified two new splice variants, V4 and V5. V4 encodes a membrane-bound isoform and V5 a secreted one. While V4 expression was ubiquitous, V5 was only in prostate. The analysis revealed no V1. CMG2 488 and 489 showed broad expression, but 322 transcript showed tissuespecific and developmental expression. No tissue tested had 386 transcript. PCR also revealed a new transcript of CMG2 that encodes a 480-residue membrane-bound protein, and that showed selective expression. The only two variants that showed correlational expression with cancer or normal phenotype were TEM8 V2, present in twice as many normal tissues as cancer, and CMG2-322, present in twice as many cancer tissues as normal. All other transcripts had broad expression, except TEM8 V1 and CMG2-386, which were absent from all tissues. As anthrax toxin receptors, TEM8 V4 is functional, CMG2-480 is not. Overall, this analysis helps determine which receptors the toxin uses to harm various tissues. It also serves as a broad repertoire of TEM8 and CMG2 expression in normal tissues for comparison with abnormal states.


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Integrative Biology