Protein level of apolipoprotein E increased in human hepatocellular carcinoma

Yokoyama, Yuichiro; Kuramitsu, Yasuhiro; Takashima, Motonari; Iizuka, Norio; Terai, Shuji; Oka, Masaaki; Nakamura, Kazuyuki; Okita, Kiwamu; Sakaida, Isao

doi:10.3892/ijo.28.3.625

Cited by 21 publications

(20 citation statements)

References 34 publications

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“…Both Apo A-1 and Apo A-2 have been reported to be differentially expressed in HCC patients, and treated as potential biomarkers. (27,28) ApoE was illustrated as overexpression in the multiple cases family member group, and this protein has already shown upregulated expression in various cancers such as liver, (29,30) brain, (31) and ovary. (32) Although the association between ApoE and carcinogenesis remains unclear, we suspected ApoE may function through modulating immune system like suppressing T cell proliferation, and regulating inflammation as well as oxidation.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

Zhong

Ning

et al. 2012

Cancer Science

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Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432. 94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC. (Cancer Sci 2012; 103: 1833-1838 H epatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers, and ranks the third cause of cancer related death in the world (9.2% of the total).(1,2) Among different geographical regions, large variation of morbidity and risk factors were observed, with the highest rate in Asian, and lowest rate in the US as well as Europe countries.(3,4) Hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and chronic exposure to aflatoxin play crucial roles in hepatocarcinogenesis among Asian people, while fatty liver disease and high consumption of alcohol are the dominant causes among low incidence regions.(5,6) The HCC incidence rate is remarkably high in China, accounting for approximately 55% of annual new cases in the world.(7) Particularly in Guangxi province of China, an endemic area of HBV infection, the HCC mortality has risen as the first cause of malignant cancer-relative death. (8) It is well-accepted that HBV infection constitutes the main etiological factor of HCC, while the process of hepatocarcinogenesis integrates multi-stages and multi-factors, including interactions of HBV, chemical carcinogen, and genetic susceptibility.(9) In addiction, the literature conveys that the lifetime risk of developing HCC for HBV infected individuals has been estimated to be 40%, (10) implying that a wide individual discrepancy exists in the HCC susceptibility, and that environmental factors alone are insufficient to fully address the familial aggregation of HCC. (11,12) We have observed that most HCC occurs obviously in clusters by geographical distribution or by family aggregation in Guangxi, China. Family aggregation of HCC has received researchers' attention for decades. Pedigree studies are frequently carried out to val...

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Section: Discussionmentioning

confidence: 99%

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

Zhong

Ning

et al. 2012

Cancer Science

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“…The changes that occur in hepatocyte apoE trafficking under pathological conditions associated with oxidative stress are not well understood. It has been reported that there is impaired secretion and intracellular accumulation of apoE in both ageing hepatocytes 17 and tumours of the liver 18 . This suggests that impaired apoE trafficking may be a feature of liver pathology.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that there is impaired secretion and intracellular accumulation of apoE in both ageing hepatocytes 17 and tumours of the liver. 18 This suggests that impaired apoE trafficking may be a feature of liver pathology. To investigate this hypothesis, the effects of H 2 O 2 on apoE trafficking were studied.…”

Section: Discussionmentioning

confidence: 99%

Effects of hydrogen peroxide and apolipoprotein E isoforms on apolipoprotein E trafficking in HepG2 cells

Sabaretnam

Harris

Kockx

et al. 2009

Clin Exp Pharma Physio

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1. The major source of apolipoprotein E (apoE) is the liver. In the present study, the effects of oxidative stress and apoE isoforms on apoE distribution and trafficking were established using the HepG2 liver tumour cell line. 2. Hydrogen peroxide (0, 25, 250 and 1000 micromol/L) was associated with rapid and concentration-dependent redistribution of apoE into the early endosomal compartment. This redistribution was achieved with a much lower concentration (25 micromol/L) than that needed to induce changes in intracellular apoE mRNA expression, apoE protein levels and markers of oxidative stress (250-1000 micromol/L). 3. Live cell imaging of apoE3-green fluorescent protein revealed a significant decrease in traffic velocity in response to oxidative stress. 4. The E4 isoform was associated with reduced trafficking velocity compared with the E3 isoform under basal conditions. 5. The results indicate that oxidative stress and apoE isoforms influence apoE trafficking and distribution within HepG2 cells. Altered apoE hepatocyte trafficking may provide a mechanistic link between oxidative stress, ageing and some diseases in older people.

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“…Higher serum levels of APOE were related to the progression of breast cancer and poor prognosis in the patients . APOE protein was frequently elevated in HCC tissues and might be a suitable histological marker for HCC …”

Section: Apolipoproteins and Cancermentioning

confidence: 99%

Apolipoproteins and cancer

et al. 2019

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The role of apolipoproteins in cardiovascular disease has been well investigated, but their participation in cancer has only been explored in a few published studies which showed a close link with certain kinds of cancer. In this review, we focused on the function of different kinds of apolipoproteins in cancers, autophagy, oxidative stress, and drug resistance. The potential application of apolipoproteins as biomarkers for cancer diagnosis and prognosis was highlighted, together with an investigation of their potential as drug targets for cancer treatment. Many important roles of apolipoproteins and their mechanisms in cancers were reviewed in detail and future perspectives of apolipoprotein research were discussed.

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Protein level of apolipoprotein E increased in human hepatocellular carcinoma

Cited by 21 publications

References 34 publications

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

Effects of hydrogen peroxide and apolipoprotein E isoforms on apolipoprotein E trafficking in HepG2 cells

Apolipoproteins and cancer

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