| Title |
PRKAR1A overexpression is associated with increased ECPKA autoantibody in liver fluke-associated cholangiocarcinoma: application for assessment of the risk group
|
|---|---|
| Published in |
Tumor Biology, August 2012
|
| DOI | 10.1007/s13277-012-0491-3 |
| Pubmed ID | |
| Authors |
Watcharin Loilome, Sasithorn Yooyuen, Nisana Namwat, Paiboon Sithithaworn, Anucha Puapairoj, Junko Kano, Masayuki Noguchi, Masanao Miwa, Puangrat Yongvanit |
| Abstract |
Cholangiocarcinoma (CCA) associated with Opisthorchis viverrini (Ov) chronic infection is the most frequent primary liver cancer in Thailand, and current approaches to early diagnosis and curative treatments are largely disappointing. We hypothesize a role for protein kinase A (PKA) in Ov-induced CCA. First, we studied the PKA isozyme switching in the liver from the hamster CCA model using quantitative (q) PCR, in situ hybridization, and immunohistochemical and western blot analysis. Second, the presence of extracellular PKA (ECPKA) in CCA cell lines and their conditioned media was demonstrated by western blot and PKA activity assay. Third, we determined the association between PRKAR1A expression and serum ECPKA autoantibody in patients with CCA by ELISA. We demonstrated that an increased PRKAR1A expression is restricted to the biliary cells starting from week 1, with remarkable up-regulation when CCA has completely developed by week 24. The switching of the PKA regulatory subunit isoforms from PRKAR2B/PKAII to PRKAR1A/PKAI is significantly associated with cholangiocyte proliferation. Further, we observed that human CCA cell lines express PRKAR1A but not PRKAR2B and excrete ECPKA. Finally, ECPKA autoantibodies are detected in serum of patients with CCA, adenocarcinoma, and Ov infection with periductal fibrosis, but not from Ov-infected subjects without periductal fibrosis lesion and healthy controls. We conclude that PKA isozyme switching and the PRKAR1A/PKAI pathway might contribute to the induction of cholangiocyte transformation and proliferation in Ov-induced CCA. Overexpression of PRKAR1A leads to secretion of ECPKA which is associated with serum autoantibody that may constitute a biomarker for human CCA genesis. |
Mendeley readers
The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Russia | 1 | 8% |
| Unknown | 12 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Lecturer | 2 | 15% |
| Researcher | 2 | 15% |
| Student > Bachelor | 1 | 8% |
| Professor | 1 | 8% |
| Student > Master | 1 | 8% |
| Other | 3 | 23% |
| Unknown | 3 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 23% |
| Agricultural and Biological Sciences | 2 | 15% |
| Environmental Science | 1 | 8% |
| Veterinary Science and Veterinary Medicine | 1 | 8% |
| Nursing and Health Professions | 1 | 8% |
| Other | 1 | 8% |
| Unknown | 4 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2012.
All research outputs
#20,167,959
of 22,679,690 outputs
Outputs from Tumor Biology
#1,833
of 2,621 outputs
Outputs of similar age
#151,675
of 169,487 outputs
Outputs of similar age from Tumor Biology
#16
of 16 outputs
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