Basic–Liver, Pancreas, and Biliary TractEpigenetic Inhibition of Nuclear Receptor Small Heterodimer Partner Is Associated With and Regulates Hepatocellular Carcinoma Growth
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HCC Specimens and Cell Lines
HCC specimens were obtained through the National Cancer Institute Cooperative Human Tissue Network and the Liver Tissue Procurement and Distribution System (Minneapolis, Minnesota). Institutional Review Board was approved by the University of Kansas Medical Center human subjects committee. HCC cell lines were obtained from the American Type Culture Collection (Manassas, VA) (HepG2, HB-8065; Hep3B, HB-8064) and the Health Science Research Resources Bank (Saito-Asagi, Osaka, Japan) (Huh7, JCRB
Epigenetic Repression of the SHP Gene in HCC Specimens
To determine if diminished SHP mRNA expression occurs in HCC, we determined the SHP expression profile in 10 pairs of normal human liver and HCC pathologic specimens by Northern blot. The analysis revealed that the expression of SHP mRNA was down-regulated in 9 of 10 HCC specimens as compared with the normal surrounding liver tissue (Figure 1A, left). We further confirmed a correlated down-regulation of SHP protein levels in HCC specimens using immunohistochemistry analysis (Figure 1A, right,
Discussion
HCC often is diagnosed at an advanced stage when therapies have a limited efficacy.23 The fact that HCC is resistant to conventional chemotherapy leaves advanced disease with few therapeutic options and dismal prognosis. The challenges with early diagnosis of HCC emphasize the need for better biomarkers for early stage HCC. HCC tumors are phenotypically and genetically heterogeneous tumors and usually emerge in the presence of chronic liver disease, including hepatitis B or C, and metabolic
References (29)
The peroxisome proliferator-activated receptor alpha (PPARalpha): role in hepatocarcinogenesis
Mol Cell Endocrinol
(2002)- et al.
Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers
Gastroenterology
(2006) - et al.
Role of nuclear receptors in lung tumourigenesis
Eur J Cancer
(2005) - et al.
MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
Cancer Cell
(2004) - et al.
Molecular targets and the treatment of myeloid leukemia
Mol Genet Metab
(2006) - et al.
The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes
Cell Metab
(2005) - et al.
CpG islands as gene markers in the human genome
Genomics
(1992) DNA methylation and histone modifications: teaming up to silence genes
Curr Opin Genet Dev
(2005)- et al.
Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner
J Biol Chem
(2002) - et al.
Transcriptional corepression by SHP: molecular mechanisms and physiological consequences
Trends Endocrinol Metab
(2005)
Molecular regulation of androgen action in prostate cancer
J Cell Biochem
Progestins and breast cancer
Breast Dis
Mechanical agitation induces gene expression of NOR-1 and its closely related orphan nuclear receptors in leukemic cell lines
Leukemia
Nuclear receptorsI. PPAR gamma in the gastrointestinal tract: gain or pain?
Am J Physiol
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Supported by a Liver Scholar Award from the American Liver Foundation/American Association for the Study of Liver Diseases, a Junior Faculty Award from the American Diabetes Association, and a BGIA Award from the American Heart Association (L.W.). The Flow Cytometry Core is supported in part by a National Institutes of Health grant (P20 RR016443) from NCRR. HCC specimens were obtained through the Liver Tissue Procurement and Distribution System, which was funded by National Institutes of Health contract N01-DK-9-2310.