Altered HOX and WNT7A expression in lung cancer

Roser Calvo, James West, Wilbur Franklin, Paul Erickson, Lynne Bemis, Efang Li, Barbara Helfrich, Paul Bunn, Joelle Roche, Elisabeth Brambilla, Rafael Rosell, Robert M. Gemmill, Harry A. Drabkin

Research output: Contribution to journalArticle

171 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)12776-12781
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number23
DOIs
StatePublished - Jan 1 2000

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Lung Neoplasms
Catenins
Leukemia
Cell Line
Cell Polarity
Fibroblast Growth Factors
Loss of Heterozygosity
Mesothelioma
Tumor Cell Line
Genes
Reverse Transcription
Real-Time Polymerase Chain Reaction
Transcription Factors
Chromosomes
Epithelial Cells
Maintenance
Cell Proliferation
RNA
Gene Expression
Lung

Keywords

  • HOXA1
  • HOXA10
  • HOXA7
  • HOXA9
  • HOXB9

Cite this

Altered HOX and WNT7A expression in lung cancer. / Calvo, Roser; West, James; Franklin, Wilbur; Erickson, Paul; Bemis, Lynne; Li, Efang; Helfrich, Barbara; Bunn, Paul; Roche, Joelle; Brambilla, Elisabeth; Rosell, Rafael; Gemmill, Robert M.; Drabkin, Harry A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 23, 01.01.2000, p. 12776-12781.

Research output: Contribution to journalArticle

Calvo, R, West, J, Franklin, W, Erickson, P, Bemis, L, Li, E, Helfrich, B, Bunn, P, Roche, J, Brambilla, E, Rosell, R, Gemmill, RM & Drabkin, HA 2000, 'Altered HOX and WNT7A expression in lung cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 23, pp. 12776-12781. https://doi.org/10.1073/pnas.97.23.12776
Calvo, Roser ; West, James ; Franklin, Wilbur ; Erickson, Paul ; Bemis, Lynne ; Li, Efang ; Helfrich, Barbara ; Bunn, Paul ; Roche, Joelle ; Brambilla, Elisabeth ; Rosell, Rafael ; Gemmill, Robert M. ; Drabkin, Harry A. / Altered HOX and WNT7A expression in lung cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 23. pp. 12776-12781.
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AU - West, James

AU - Franklin, Wilbur

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AU - Li, Efang

AU - Helfrich, Barbara

AU - Bunn, Paul

AU - Roche, Joelle

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