Role of miRNA in distinguishing primary brain tumors from secondary tumors metastatic to the brain.

Cancer is the result of complex processes that involve multiple molecular alterations. The understanding of such complexity has been improved by the advent of a new class of small, noncoding RNA gene products known as microRNAs (or miRNAs). miRNAs play an essential role in cancer development and progression by modulating gene expression binding to target mRNA, causing either mRNA degradation or translation inhibition. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. Beyond these valuable features, miRNAs could be potentially used in the future as innovative and targeted therapeutics. Recent in vitro and expression profiling studies have identified that specific miRNAs are directly involved in brain carcinogenesis and in the metastatic process. This review focuses on metastasis-related miRNAs and on the role of miRNAs in distinguishing between primary and metastatic brain tumors. In clinical practice, miRNAs could represent a promising new class of cancer biomarkers in the diagnosis and management of brain neoplastic lesions.

Arylamine N-acetyltransferase-1 is highly expressed in breast cancers and conveys enhanced growth and resistance to etoposide in vitro.

Comparative two-dimensional proteome analysis was used to identify proteins differentially expressed in multiple clinical normal and breast cancer tissues. One protein, the expression of which was elevated in invasive ductal and lobular breast carcinomas when compared with normal breast tissue, was arylamine N-acetyltransferase-1 (NAT-1), a Phase II drug-metabolizing enzyme. NAT-1 overexpression in clinical breast cancers was confirmed at the mRNA level and immunohistochemical analysis of NAT-1 in 108 breast cancer donors demonstrated a strong association of NAT-1 staining with estrogen receptor-positive tumors. Analysis of the effect of active NAT-1 overexpression in a normal luminal epithelial-derived cell line demonstrated enhanced growth properties and etoposide resistance relative to control cells. Thus, NAT-1 may not only play a role in the development of cancers through enhanced mutagenesis but may also contribute to the resistance of some cancers to cytotoxic drugs.