Lung cancer is the leading cause of cancer-related death in the United States and metastatic behavior is largely responsible for this mortality. Mutations in multiple “driver” oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is down-regulated in epithelial tumors including lung cancer and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, while re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits TGFβ-activated MAPK and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT, and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach.

To date, only a small percentage of human genes have been cloned and mapped. To facilitate more rapid gene mapping and disease gene isolation, chromosome S-specific cDNA libraries have been constructed from five sources. DNA sequencing and regional mapping of 205 unique cDNAs indicates that 25 are from known chromosome S genes and 138 are from new chromosome S genes (a frequency of 79.5%}. Sequence complexity estimates indicate that each library contains -20% of the -SO00 genes that are believed to reside on chromosome 5. This study more than doubles the number of genes mapped to chromosome S and describes an important new tool for disease gene isolation.

Systemic lupus erythematosus (SLE) is a chronic autoimmune connective tissue disease characterized by the production of a large number of autoantibodies, but the etiology is complex and poorly understood. A range of different platforms have served as screening methods for the determination of autoantibody specificities over the past few decades. Proteomic microarray is a relatively new high-throughput technology which is playing an increasingly important role in autoantibody diagnostics. In this article, we review different platforms for assaying autoantibodies in SLE, and highlight the use of autoantigen arrays as powerful tools for autoantibody exploration in SLE.