Expression of β-catenin in hepatocellular carcinoma

Tien, Liem Thanh; Ito, Masahiro; Nakao, M; Niino, Daisuke; Serik, Meirmanov; Nakashima, Masahiro; Wen, Chun-Yang; Yatsuhashi, Hiroshi; Ishibashi, Hiromi

doi:10.3748/wjg.v11.i16.2398

Cited by 55 publications

(40 citation statements)

References 21 publications

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“…In the liver CK19 is known to be a marker of dedifferentiation (51), which showed a positive correlation with other embryonic/ development markers such as cytoplasmatic ß-catenin, PDX-1 and PTC. Surprisingly, the mesenchymal marker vimentin was negatively associated with the progenitor markers CD34 and cytoplasmatic ß-catenin, which was generally not the case in other studies (30,31). In line with the literature, and thereby indicating the association of progenitor potency and embryonic dedifferentiation, CD34 and Thy-1 were linked to the embryonic/developmental markers PDX-1 and ß-catenin and vice versa (52)(53)(54).…”

Section: ) -------------------------------------------------supporting

confidence: 68%

“…Literature on WNT-pathway gives evidence that a more membranous expression of ß-catenin is associated with better grading and outcome of HCC (28)(29)(30)(31). Membranous ß-catenin expression was mainly found in Huh-7, Hep3B and Hep3B-MG, whereas cytoplasmatic ß-catenin was especially high in HepG2 cells, which was also associated with another embryonic marker PDX-1.…”

Section: Discussionmentioning

confidence: 99%

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Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Jabari

Meissnitzer²,

Quint³

et al. 2009

Int J Oncol

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Abstract. Tumor cells have the capability to trans-and to dedifferentiate, for example by reactivating embryonic development genes and stem cell characteristics. The aim of our study was to show the differential expression of stem-and progenitor cell markers in human hepatocellular carcinoma cell lines (HCC). Different human HCC cell lines (HUH7, HUH7 5-15, HUH7 pcDNA3.1, Hep3B and HepG2) were cultured under standard conditions in vitro or implanted subcutaneously (5x10 6 cells) in male NMRI mice. Specimens were characterized by quantitative real-time PCR, Western blotting, methylation-specific PCR and immunohistochemistry for markers of differentiation (cytokeratins, vimentin), embryonic development or stem cells (PTC, PDX-1, SHH, Thy1, c-kit, CD34, ß-catenin, Ki-67). The investigated HCC cell lines showed different patterns of marker expression allowing to distinguish four distinct groups: the classical cholangiocellular type (Huh-7, Huh-7 pcDNA3.1, Hep3B) with expression of CK7/19, ß-catenin and CD34; a dedifferentiated mesenchymal-proliferative type (Huh-7 5-15) characterized by CK19, Vimentin and Ki-67; a dedifferentiated embryonic-development type (Hep3B implanted in matrigel) with expression of CK19, ß-catenin and PTC and a classical HCC type (HepG2) showing CK18/19 and ß-catenin expression. HCC cell lines showed significantly different expression patterns of differentiation markers in a xenograft model. Furthermore, direct association of some markers was observed. The groups differ from each other in expression patterns, but also show that environmental factors play an important role in the behaviour of cells.

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Section: ) -------------------------------------------------supporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Jabari

Meissnitzer²,

Quint³

et al. 2009

Int J Oncol

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show abstract

“…Hepatitis B virus is a common causal agent of liver cancer, and other factors have also been found. However, the molecular mechanisms contributing to tumor progression to HCC remain unknown [1] . In recent years, targeted therapies for a variety of HCCs have achieved clinically significant response rates and have given oncologists the chance to develop individualbased strategies for patient therapy.…”

Section: Introductionmentioning

confidence: 99%

Rab23 is a potential biological target for treating hepatocellular carcinoma

Liu

Wang²,

Li³

et al. 2007

WJG

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in HCC. Rab23 may be both a HCC predictor and a target for treating HCC. INTRODUCTIONHepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver. HCC is the third leading global cause of cancer-related death. Over 54% of HCC cases occur in China. Hepatitis B virus is a common causal agent of liver cancer, and other factors have also been found. However, the molecular mechanisms contributing to tumor progression to HCC remain unknown [1] . In recent years, targeted therapies for a variety of HCCs have achieved clinically significant response rates and have given oncologists the chance to develop individualbased strategies for patient therapy. One rationale for such therapeutic approaches is to detect target molecules in the tumor. There is a growing list of such target molecules, the levels of which are now routinely estimated by IHC staining in biopsy specimens or surgically removing tumor material. Such assays not only generate important data for therapeutic decisions, but also provide information relevant to the prognosis of patients [2] . An example is targeting of the hedgehog (Hh) pathway. Dysregulation of this pathway has been implicated in the genesis of cancers from multiple tissue types [3] . Moreover, from embryogenesis to adulthood, skin and gastrointestinal progenitors are regulated by Hh signaling [4][5][6] . This pathway is activated when sonic hedgehog (SHH) or Indian hedgehog (IHH) ligands bind to their receptor, patched (PTC). When unoccupied by ligand, PTC is a tumor suppressor that binds to and represses smoothened (SMO) [7] , preventing the SMO proto-oncoprotein from LIVER CANCERRab23 is a potential biological target for treating hepatocellular carcinoma

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“…The Wnt proteins are a family of secreted glycoproteins that govern cell proliferation, migration, differentiation and polarity among cells during embryoge- [67,68]. Mutations in this pathway have been shown to be associated with several forms of hereditary and sporadic cancer both in the intestine and the liver [24,64,69,70].…”

Section: Signaling In Tissue Repair and Regenerationmentioning

confidence: 99%

“…Cancer has therefore been described as a "wound that does not heal" or perhaps more appropriately, "the wound is a tumor that heals itself" [21,22]. The association between cancer and persistent inflammatory or regenerative states may be a reflection of this possibility [23][24][25]. Moreover, highly conserved morphogen signaling pathways such as Wnt/β-catenin, Hedgehog, Jagged/Notch, FGFs, and the BMP/TGF-β superfamilies are all recapitulated in the process of postnatal tissue restoration, and when dysregulated, perhaps initiate carcinogenesis.…”

mentioning

confidence: 99%

Repair and regeneration: opportunities for carcinogenesis from tissue stem cells

Perryman

Sylvester

2006

Journal of Cellular and Molecular Medicine

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This review will discuss the mechanisms of repair and regeneration in various tissue types and how dysregulation of these mechaisms may lead to cancer. Normal homeostasis involves a careful balance between cell loss and cell renewal. Stem and progenitor cells perform these biologic processes as the functional units of regeneration during both tissue homeostasis and repair. The concept of tissue stem cells capable of giving rise to all differentiated cells within a given tissue led to the concept of a cellulr hierarchy in tissues and in tumors. Thus, only a few cells may be necessary and sufficient for tissue repair or tumor regeneration. This is known as the hierarchical model of tumorigenesis. This report will compare this model with the stochastic model of tumorigenesis. Under normal circumstances, the processes of tissue regeneration or homeostasis are tightly regulated by several morphogen pathways to prevent excessive or inappropriate cell growth. This review presents the recent evidence that dysregulation of these processes may provide opportunities for carcinogenesis for the long-lived, highly proliferative tissue stem cell population. New findings of cancer initiating tissue stem cells identified in several solid and circulating cancers including breast, brain hematopoietic tumors will also be reviewed. Finally, this report reviews the cellular biology of cancer and its relevance to the development of more effective cancer treatment protocols.

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Expression of β-catenin in hepatocellular carcinoma

Abstract: The beta-catenin expression in HCC cells was heterogeneous among types of hepatitis viral infection. Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background.

Cited by 55 publications

References 21 publications

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Rab23 is a potential biological target for treating hepatocellular carcinoma

Repair and regeneration: opportunities for carcinogenesis from tissue stem cells

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