Altered expression of KCNK9 in colorectal cancers.
K(+) channels have been reported to be involved in the proliferation of many types of cells, including some human carcinoma and tumor cell lines. KCNK9, a TASK channel, is amplified and overexpressed in several types of human cancer. In the present study, we examined the expression and somatic mutations of KCNK9 in 124 colorectal cancers by immunohistochemistry using tissue microarray and PCR-SSCP. Immunopositivity was observed in 57 (46.0%) of 124 colorectal cancers. Clinically, KCNK9 was immunopositive in 4 (30.7%) of 13 cases which were stage A, 26 (55.3%) of 47 which were stage B, 23 (41.1%) of 56 which were stage C, and 4 (50%) of 8 which were stage D. Statistically, KCNK9 protein expression was not related to tumor stage (Bartholomew test, p>0.05) and lymph node metastasis (Chi-Square test, p=0.8338). In the mutation study of the KCNK9 gene, we found only one sequence variation (ACG-->ACC, Thr-->Thr) at codon 170 both in corresponding normal and tumor DNAs. These results indicate that overexpression rather than mutation of the KCNK9 gene may contribute to the development of colorectal cancers and suggest that the development of KCNK9-targeted agents may provide new possibilities in the treatment of colorectal cancer.
Kim
Chang Jae
CJ
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, Korea.
Cho
Yong Gu
YG
Jeong
Seong Whan
SW
Kim
Young Sil
YS
Kim
Su Young
SY
Nam
Suk Woo
SW
Lee
Sug Hyung
SH
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Park
Won Sang
WS
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain