Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo
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We have studied the gene expression pattern of invasive primary mammary tumor cells using a unique in vivo invasion assay that isolates the invasive tumor cells by chemotaxis. One of the genes upregulated in the invasive tumor cells is Mena, an actin binding protein involved in the regulation of cell motility. There are multiple known splice variants of Mena accounted for by four alternatively included exons, +, ++, +++ and 11a. Using the in vivo invasion assay in rats and mice with mammary tumors we observed that two isoforms of Mena, ++ and +++, are upregulated in the invasive tumor cells and one isoform, 11a, is downregulated. The Mena isoform switching pattern described here may provide a new biomarker for the presence of metastatic cancer cells and for prognosis.
KeywordsBreast cancer Metastasis Biomarker Mena Splice variant
The authors wish to acknowledge Andrew Freidman for technical help, Drs Erik Sahai and Jeffrey Segall for their help in discussions. U.P. was supported by the Anna Fuller Molecular Oncology Fund and the Ludwig Center for Molecular Oncology. This work is supported by NIH CA 100324 (SG and JC) and CA113395 (JC), NIH grant # GM58801 and ICBP grant # 1-U54-CA112967 for FBG, Lega Italiana per la Lotta Contro i Tumori and Associazione Italiana per la Ricerca sul Cancro (AIRC) for PN. SG is the recipient of the Young Investigator Award from Breast Cancer Alliance Inc.
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