Abstract
The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse transcription-PCR (RT-PCR), followed by cloning and sequencing. Eight of 14 biopsy tissues obtained from advanced HCC, 6 of 13 surgically removed HCC tissues, and 2 of the adjacent noncancerous tissues contained aberrant KAP transcripts. Using the yeast two-hybrid system, five of seven representative KAP mutants were shown to be defective in interacting with Cdk2. These data suggest a possible role of KAP mutations in multiple-step hepatocarcinogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 4697-4700 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 60 |
| Issue number | 17 |
| State | Published - 01 09 2000 |
| Externally published | Yes |
Keywords
- Amino Acid Sequence
- CDC2-CDC28 Kinases
- Carcinoma, Hepatocellular/enzymology
- Carcinoma, Hepatocellular/genetics
- Cell Cycle Proteins
- Cyclin-Dependent Kinase 2
- Cyclin-Dependent Kinase Inhibitor Proteins
- Cyclin-Dependent Kinases/metabolism
- Dual-Specificity Phosphatases
- Female
- Hepatitis B, Chronic/enzymology
- Hepatitis B, Chronic/genetics
- Hepatitis C, Chronic/enzymology
- Hepatitis C, Chronic/genetics
- Humans
- Liver Neoplasms/enzymology
- Liver Neoplasms/genetics
- Liver/enzymology
- Liver/physiology
- Male
- Middle Aged
- Molecular Sequence Data
- Mutation
- Protein Tyrosine Phosphatases/biosynthesis
- Protein Tyrosine Phosphatases/genetics
- Protein Tyrosine Phosphatases/metabolism
- Protein-Serine-Threonine Kinases/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
