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 language | English (US) |
|---|---|
| Pages (from-to) | 12776-12781 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 97 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jan 1 2000 |
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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 journal › Article
}
TY - JOUR
T1 - Altered HOX and WNT7A expression in lung cancer
AU - Calvo, Roser
AU - West, James
AU - Franklin, Wilbur
AU - Erickson, Paul
AU - Bemis, Lynne
AU - Li, Efang
AU - Helfrich, Barbara
AU - Bunn, Paul
AU - Roche, Joelle
AU - Brambilla, Elisabeth
AU - Rosell, Rafael
AU - Gemmill, Robert M.
AU - Drabkin, Harry A.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
KW - HOXA1
KW - HOXA10
KW - HOXA7
KW - HOXA9
KW - HOXB9
UR - http://www.scopus.com/inward/record.url?scp=0033731796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033731796&partnerID=8YFLogxK
U2 - 10.1073/pnas.97.23.12776
DO - 10.1073/pnas.97.23.12776
M3 - Article
C2 - 11070089
AN - SCOPUS:0033731796
VL - 97
SP - 12776
EP - 12781
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -