TY - JOUR
T1 - Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas
AU - Gunduz, Mehmet
AU - Nagatsuka, Hitoshi
AU - Demircan, Kadir
AU - Gunduz, Esra
AU - Cengiz, Beyhan
AU - Ouchida, Mamoru
AU - Tsujigiwa, Hidetsugu
AU - Yamachika, Eiki
AU - Fukushima, Kunihiro
AU - Beder, Levent
AU - Hirohata, Satoshi
AU - Ninomiya, Yoshifumi
AU - Nishizaki, Kazunori
AU - Shimizu, Kenji
AU - Nagai, Noriyuki
N1 - Funding Information:
This work was supported by grant-in-aid for scientific research A from the Ministry of Education, Culture, Sports, Science and Technology to N Nagai (#15209060).
PY - 2005/8/15
Y1 - 2005/8/15
N2 - We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer.
AB - We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer.
KW - HNSCC
KW - ING family
KW - ING1
KW - LOH
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U2 - 10.1016/j.gene.2005.02.014
DO - 10.1016/j.gene.2005.02.014
M3 - Article
C2 - 15935570
AN - SCOPUS:23844441255
SN - 0378-1119
VL - 356
SP - 109
EP - 117
JO - Gene
JF - Gene
IS - 1-2
ER -