ALTERED HOX AND WNT7A EXPRESSION IN HUMAN LUNG CANCER

摘要

Alterations in HOX expression have been clearly implicated in leukemia, but their role in most other malignant diseases remains unknown. The present disclosure reports that specific member of the HOX gene family, HOXA9, HOXA10, and HOXB9 are overexpressed in lung cancer cells using are using real-time quantitative assays. In some cases, marked HOX overexpression was associated with elevated FGF10 and 17. During development, the WNT pathway affects cell fate, polarity and proliferation, and WNT7a has been implicated in the maintenance of HOX expression. In contrast to normal lung and mortal short-term bronchial epithelial cultures, WNT7a was frequently reduced or absent in lung cancers. In immortalized bronchial epithelial cells, WNT7a was lost concomitantly with HOXA1, and a statistically significant correlation between the expression of both genes was observed in lung cancer cell lines. Furthermore, we identified a homozygous deletion of beta -catenin in the mesothelioma, NCI-H28, associated with reduced WNT7A and the lowest overall cell line expression of HOXA1, A7, A9 and A10 while HOXB9 levels were unaffected. Of note, both WNT7a and beta-catenin are encoded on 3p which undergoes frequent loss in these tumors. Our results indicate that alterations in regulatory circuits involving HOX, WNT, and FGF pathways occur frequently in lung cancer.