Altered expression of splicing factor, heterogeneous nuclear ribonucleoprotein A2/B1, in mouse lung neoplasia

摘要: Our previous proteomic investigation of lung neoplasia in vitro demonstrated a high concentration the cancer biomarker and splicing factor, hnRNP A2/B1, transformed mouse epithelial cell line, E9. Since changes pre-mRNA profoundly affect neoplastic progression, we examined A2/B1 expression chemically induced primary tumors, an vivo model pulmonary adencocarcinoma. Tumor content spatial distribution assessed by immunohistochemistry varied with stage genetic background, whether tumors were single agent (urethane) or 2-stage initiation/promotion (3-methylcholanthrene/butylated hydroxytoluene) carcinogenesis. To address mechanisms governing changes, utilized models. protein was overexpressed E9, spontaneous tranformant immortalized but non-neoplastic E10 cells, not strictly function enhanced proliferative rate cells. Elevated mRNA positively associated division both levels decreased proliferating The increased reflected stability, as shown measuring time-dependent decay after inhibiting transcription. Dysregulation during thus depends on complex gene–environmental interactions that type-specific processing and, most probably, rates translation and/or degradation. © 2007 Wiley-Liss, Inc.