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Increased Expression of the Pre-mRNA Regulating Gene SRp20 in Primary Breast Cancer is Associated with Metastasis to Axillary Lymph Node

並列摘要


Cancer progression, including tumor metastasis, is manifested as a mutator phenotype. The survival of genetically unstable and phenotypically heterogeneous metastatic tumor cells, however, cannot be exclusively mediated by irreversible mutation affecting the DNA level. Transcriptional mechanisms, such as pre-MRNA splicing regulated by SR proteins, which can flexibly regulate gene expression leading to the formation of different mRNA forms depending on the cellular microenvironment, may act as alternative mutators linked to tumor metastasis. We hypothesized that the SR genes, a major gene family encoding nuclear phosphoproteins with serine- arginine (SR)-rich domains that regulate pre-mRNA splicing, might be associated with metastasis. Sixty breast cancers, including 35 tumors manifesting lymph node metastasis (LNM), were assayed for SR gene expression by RT-PCR, which was then examined for an association with LNM. Support for our hypothesis comes from the observation that increased expression of SRp20, the SR family member with the lowest molecular weight and lowest fidelity in regulating transcription, was found to be highly associated with LNM (p<0.05). Increased expression of SRp20 occurred early during tumor progression, since it was detectable in 50% of normal breast tissues neighboring breast tumors, and persisted in the primary tumor, subsequently leading to LNM. These findings support that increased expression of SRp20 might serve as a mutator predisposing breast cancer patients to develop LNM.

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