Abstract
Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located at chromosome 18q21. However, DCC gene was found to have few somatic mutations and the heterozygous mice (DCC+/-) showed a similar frequency of tumor formation compared with the wild-type mice (DCC +/+). Recently, DCC came back to the spotlight as a better understating of its function and relationship with its ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation was found in 75% of primary HNSCC. There was a significant correlation between DCC promoter region hypermethylation and DCC expression (assessed by immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5-aza-2′- deoxycytidine (a demethylating agent) and reexpression of DCC was noted. Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete abrogation of growth in all cell lines, whereas additional cotransfection of netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC.
| Original language | English |
|---|---|
| Pages (from-to) | 9401-9407 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 19 |
| DOIs | |
| State | Published - Oct 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Deleted in colorectal cancer is a putative conditional tumor-suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma. / Carvalho, André Lopes; Chuang, Alice; Jiang, Wei Wen; Lee, Juna; Begum, Shahnaz; Poeta, Luana; Zhao, Ming; Jerónimo, Carmen; Henrique, Rui; Nayak, Chetan; Park, Hannah L.; Brait, Mariana R O; Liu, Chunyan; Zhou, Shaoyu; Koch, Wayne; Fazio, Vito Michele; Ratovitski, Edward; Trink, Barry; Westra, William; Sidransky, David; Moon, Chul So; Califano, Joseph A.
In: Cancer Research, Vol. 66, No. 19, 01.10.2006, p. 9401-9407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Deleted in colorectal cancer is a putative conditional tumor-suppressor gene inactivated by promoter hypermethylation in head and neck squamous cell carcinoma
AU - Carvalho, André Lopes
AU - Chuang, Alice
AU - Jiang, Wei Wen
AU - Lee, Juna
AU - Begum, Shahnaz
AU - Poeta, Luana
AU - Zhao, Ming
AU - Jerónimo, Carmen
AU - Henrique, Rui
AU - Nayak, Chetan
AU - Park, Hannah L.
AU - Brait, Mariana R O
AU - Liu, Chunyan
AU - Zhou, Shaoyu
AU - Koch, Wayne
AU - Fazio, Vito Michele
AU - Ratovitski, Edward
AU - Trink, Barry
AU - Westra, William
AU - Sidransky, David
AU - Moon, Chul So
AU - Califano, Joseph A.
PY - 2006/10/1
Y1 - 2006/10/1
N2 - Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located at chromosome 18q21. However, DCC gene was found to have few somatic mutations and the heterozygous mice (DCC+/-) showed a similar frequency of tumor formation compared with the wild-type mice (DCC +/+). Recently, DCC came back to the spotlight as a better understating of its function and relationship with its ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation was found in 75% of primary HNSCC. There was a significant correlation between DCC promoter region hypermethylation and DCC expression (assessed by immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5-aza-2′- deoxycytidine (a demethylating agent) and reexpression of DCC was noted. Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete abrogation of growth in all cell lines, whereas additional cotransfection of netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC.
AB - Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located at chromosome 18q21. However, DCC gene was found to have few somatic mutations and the heterozygous mice (DCC+/-) showed a similar frequency of tumor formation compared with the wild-type mice (DCC +/+). Recently, DCC came back to the spotlight as a better understating of its function and relationship with its ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation was found in 75% of primary HNSCC. There was a significant correlation between DCC promoter region hypermethylation and DCC expression (assessed by immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5-aza-2′- deoxycytidine (a demethylating agent) and reexpression of DCC was noted. Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete abrogation of growth in all cell lines, whereas additional cotransfection of netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC.
UR - http://www.scopus.com/inward/record.url?scp=33750363705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750363705&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-1073
DO - 10.1158/0008-5472.CAN-06-1073
M3 - Article
VL - 66
SP - 9401
EP - 9407
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 19
ER -