Expression of type 2 hexokinase and mitochondria-related genes in gastric carcinoma tissues and cell lines.
BACKGROUND
The constant overexpression of glycolysis and active mitochondrial function are critical for productive energy required for the immortal proliferation of cancer cells. The genes related to glycolysis and mitochondrial respiration might have some function during stomach carcinogenesis.


METHODS
The expression of hexokinase 2 (HK2), Bcl-2 and several mitochondria-related gene products were investigated by immunohistochemistry in 257 consecutive human gastric carcinomas, and the results were compared with the clinicopathological characteristics. In addition, transcriptional change of HK2 and Bcl-2 was investigated in the hypoxic state or with mitochondrial inhibitors.


RESULTS
In immunohistochemical analysis, HK2 was overexpressed in 43 out of 257 stomach cancer patients. Bcl-2 was not expressed in cases with HK2 positive cancer tissues except for one case, while the voltage-dependent anion channel, complex II and pyruvate dehydrogenase, located in mitochondria, were expressed in all cases. The patients with HK2 expression showed a worse prognosis compared to the HK2 negative cases, and patients who were negative in Bcl-2 and positive in HK2 represented the lowest survival rate. HK2 and Bcl-2 responded to hypoxia, but not to mitochondrial dysfunction while the cellular growth was severely repressed by mitochondrial inhibitors, indicating that transcriptional regulation of HK2 and Bcl-2 proceeds upstream of dysfunctional mitochondria.


CONCLUSIONS
HK2 was overexpressed in 16.7% of gastric carcinomas, and reciprocal expression pattern with Bcl-2. The HK2 positive cases showed a worse prognosis and aggressive character.
Rho
Minsuk
M
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kim
Jin
J
Jee
Chang Do
CD
Lee
You Mie
YM
Lee
Hee Eun
HE
Kim
Min A
MA
Lee
Hye Seung
HS
Kim
Woo Ho
WH
D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006593:Hexokinase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011768:Pyruvate Dehydrogenase Complex / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D011768:Pyruvate Dehydrogenase Complex; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D006593:Hexokinase; D051057:Proto-Oncogene Proteins c-akt