In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 23 ( 2000-11-07), p. 12776-12781
Abstract:
HOX genes encode transcription factors that control
patterning and cell fates. Alterations in HOX expression have been clearly implicated in leukemia, but their role in most other malignant
diseases remains unknown. By using degenerate reverse transcription–PCR and subsequent real-time quantitative assays, we
examined HOX expression in lung cancer cell lines, direct tumor-control pairs, and bronchial epithelial cultures. As in leukemia, genes of the
HOX9 paralogous group and HOXA10 were frequently overexpressed. For HOXB9, we confirmed that elevated RNA was associated with protein
overexpression. In some cases, marked HOX overexpression was associated with elevated FGF10 and FGF17. 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 β-catenin in the mesothelioma,
NCI-H28, associated with reduced WNT7a and the lowest overall cell line expression of HOXA1, HOXA7, HOXA9, and HOXA10, whereas HOXB9 levels
were unaffected. Of note, both WNT7a and β-catenin are encoded on chromosome 3p, which undergoes frequent loss of heterozygosity in these
tumors. Our results suggest that alterations in regulatory circuits involving HOX, WNT, and possibly fibroblast growth factor pathways
occur frequently in lung cancer.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.23.12776
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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