The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

Butler, Samantha L; Dong, Huijia; Cardona, Diana; Jia, Minghong; Zheng, Ran; Zhu, Haizhen; Crawford, James M; Liu, Chen
January 2008
Laboratory Investigation (00236837);Jan2008, Vol. 88 Issue 1, p78
Hepatocyte paraffin 1 (Hep Par 1), a murine monoclonal antibody, is widely used in surgical pathology practice to determine the hepatocellular origin of neoplasms. However, identity of the antigen for Hep Par 1 is unknown. The aim of this study was to characterize the Hep Par 1 antigen. To identify the antigen, immunoprecipitation was used to isolate the protein from human liver tissue, and a distinct protein band was detected at approximately 165 kDa. The protein band was also present in small intestinal tissue, but was not present in several other non-liver tissues nor in three human hepatocellular carcinoma cell lines, Huh-7, HepG2, and LH86. The protein was purified and analyzed by mass spectrometry. It was identified as carbamoyl phosphate synthetase 1 (CPS1). CPS1 is a rate-limiting enzyme in urea cycle and is located in mitochondria. We demonstrated that hepatoid tumors (gastric and yolk sac) were immunoreactive with both Hep Par 1 antibody and anti-CPS1 antibody, further confirming the results of mass spectrometric analysis. We found that the three human hepatocellular carcinoma cell lines do not express either CPS1 RNA or protein. We confirmed that the gene was present in these cell lines, suggesting that suppression of CPS1 expression occurs at the transcriptional level. This finding may have relevance to liver carcinogenesis, since poorly differentiated hepatocellular carcinomas exhibit poor to absent immunoreactivity to Hep Par 1. In conclusion, we have identified the antigen for Hep Par 1 antibody as a urea cycle enzyme CPS1. Our results should encourage further investigation of potential role that CPS1 expression plays in liver pathobiology and carcinogenesis.Laboratory Investigation (2008) 88, 78–88; doi:10.1038/labinvest.3700699; published online 19 November 2007


Related Articles

  • Prognostic significance and potential therapeutic target of VEGFR2 in hepatocellular carcinoma. Jianfei Huang; Xialing Zhang; Qi Tang; Feng Zhang; Yuhua Li; Zhenqing Feng; Jin Zhu // Journal of Clinical Pathology;Apr2011, Vol. 64 Issue 4, p343 

    Background Vascular endothelial growth factor receptor 2 (VEGFR2) has been suggested to play an important role in solid tumours. Although several reports have shown the relationship between VEGFR2 expression and hepatocellular carcinoma (HCC), the expression pattern of VEGFR2 in HCC parenchyma...

  • Multiple regression analysis for assessing the growth of small hepatocellular carcinoma: the MIB-1 labeling index is the most effective parameter. Saito, Yoshifumi; Matsuzaki, Yasushi; Doi, Mikio; Sugitani, Takehiko; Chiba, Toshiya; Abei, Masato; Shoda, Junichi; Tanaka, Naomi; Saito, Y; Matsuzaki, Y; Doi, M; Sugitani, T; Chiba, T; Abei, M; Shoda, J; Tanaka, N // Journal of Gastroenterology;1998, Vol. 33 Issue 2, p229 

    The aim of this study was to clarify whether histological parameters reflected tumor aggressiveness in patients with hepatocellular carcinoma (HCC). The tumor volume doubling times (TVDTs) of 21 HCCs, less than 3 cm in diameter at the start of the observation period, were calculated in 21...

  • Comparative plasma membrane-associated proteomics of immortalized human hepatocytes. Lan-Tu Gou; Ai-Ping Tong; Li-Juan Chen; Ming-Hai Tang; Bin Chen; Shu-Fang Liang; Canhua Huang; Yu-Quan Wei // Biochemistry (00062979);Nov2008, Vol. 73 Issue 11, p1200 

    This work was initiated with the purpose of purifying and identifying differentially expressed plasma membrane-associated proteins between human liver cancer cell line HepG2 and normal liver cell line L02. The combined strategy of sucrose density gradient centrifugation and subsequent phase...

  • Immunohistochemical metallothionein expression in hepatocellular carcinoma: relation to tumor progression and chemoresistance to platinum agents. Endo, Tsunehiro; Yoshikawa, Masaharu; Ebara, Masaaki; Kato, Kazuki; Sunaga, Masahiko; Fukuda, Hiroyuki; Hayasaka, Akira; Kondo, Fukuo; Sugiura, Nobuyuki; Saisho, Hiromitsu // Journal of Gastroenterology;2004, Vol. 39 Issue 12, p1196 

    Background. Metallothionein (MT), which is known to detoxify heavy metal ions, is considered to serve as a mechanism of resistance to platinum complex com- pounds. In the present study, MT expression in hepatocellular carcinoma (HCC) was immunohistologically investigated to clarify its...

  • Abnormal expression of NRF-2α in hepatocellular carcinoma identified with a newly prepared monoclonal antibody against human NRF-2α protein. Ya Qing Zhang; Kai Nan Li; Ji Hong Cui; Yan Fang Liu; Shou Jing Yang // Molecular Biology Reports;Jun2011, Vol. 38 Issue 5, p3083 

    Human nuclear respiratory factor 2 alpha subunit (NRF-2α) is fundamentally important to cell function and the development. We aimed to establish the monoclonal antibody (MAb) against the human NRF-2α protein and to investigate its distribution in human hepatocellular carcinoma (HCC) and...

  • Hep88 mAb-initiated paraptosis-like PCD pathway in hepatocellular carcinoma cell line through the binding of mortalin (HSPA9) and alpha-enolase. Panadda Rojpibulstit; Suthathip Kittisenachai; Songchan Puthong; Sirikul Manochantr; Pornpen Gamnarai; Sarawut Jitrapakdee; Sittiruk Roytrakul // Cancer Cell International;2014, Vol. 14 Issue 1, p1 

    Background Hepatocellular carcinoma (HCC) is the most prevalent hepatic cancer worldwide. Currently, a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is undergoing continual development in HCC treatment. Methods In this regard, after establishing and...

  • Characterization of CD133+ parenchymal cells in the liver: Histology and culture. Yoshikawa, Seiichi; Zen, Yoh; Fujii, Takahiko; Sato, Yasunori; Ohta, Tetsuo; Aoyagi, Yutaka; Nakanuma, Yasuni; Gutiérrez-Ruiz, Maria Concepción // World Journal of Gastroenterology;10/21/2009, Vol. 15 Issue 39, p4896 

    AIM: To reveal the characteristics of CD133+ cells in the liver. METHODS: This study examined the histological characteristics of CD133+ cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133+ cells derived from human...

  • hDlk-1: a cell surface marker common to normal hepatic stem/progenitor cells and carcinomas. Nishina, Hiroshi // Journal of Biochemistry;Aug2012, Vol. 152 Issue 2, p121 

    Advances in stem cell biology have clarified that a tumour is a collection of heterogeneous cell populations, and that only a small fraction of tumour cells possesses the potential to self-renew. Delta-like 1 protein (Dlk-1) is a surface antigen present on foetal hepatic stem/progenitor cells...

  • Immunohistochemical Detection of Ras Oncogene p21 Product in Liver Cirrhosis and Hepatocellular Carcinoma. Nonomura, Akitaka; Ohta, Goroku; Hayashi, Morimoto; Izumi, Ryohei; Watanabe, Kishichiro; Takayanagi, Nobutatsu; Mizukami, Yuji; Matsubara, Fujitsugu // American Journal of Gastroenterology;Jun1987, Vol. 82 Issue 6, p512 

    Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody KAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics