The Effect of Hepatitis B Virus X Gene Expression on Response to Growth Inhibition by Transforming Growth Factor-β1

Oshikawa, Osamu; Tamura, Shinji; Kawata, Satoshi; Ito, Nobuyuki; Tsushima, Hirofumi; Kiso, Shinichi; Matsuda, Yukihiko; Yamada, Akira; Tamai, Shingo; Matsuzawa, Yūji

doi:10.1006/bbrc.1996.0819

Cited by 16 publications

(13 citation statements)

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“…Loss of sensitivity to TGF-bs has also been observed in the progression of carcinogenesis (Kiso et al, 1994;Markowitz et al, 1995;Inagaki et al, 1993;Wang et al, 1996;Park et al, 1994;Oshikawa et al, 1996;Knaus et al, 1996). It may be possible that negative control of Src kinase by TGF-bs is impaired in these tissues or cell lines, inducing Src up-regulation.…”

Section: Discussionmentioning

confidence: 98%

Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts

et al. 1998

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Section: Discussionmentioning

confidence: 98%

Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts

et al. 1998

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“…5,10,25,26 The perturbation in the postreceptor signaling pathway has been suggested to be involved in TGF-␤ resistance in some transformed cells, whereas the mechanism has not yet been well examined. Recently, we have reported that TGF-␤ 1 induces degradation of activated Src tyrosine kinase in rat fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…3 Some transformed cells, however, exhibit poor response to TGF-␤-induced growth inhibition, and this loss of negative regulation contributes to the uncontrolled proliferation of these cells. [4][5][6][7][8][9][10][11] Therefore, an enhanced understanding of the mechanisms underlying the insensitiveness to TGF-␤s greatly facilitates the development of effective strategies for preventing the progression of carcinogenesis.…”

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confidence: 99%

“…12 In most cases analyzed thus far, TGF-␤ resistance in the transformed cells is caused by altered expression of functional TGF-␤ receptors. [6][7][8][9][10][11] Whereas the perturbation in postreceptor signaling pathway has been suggested to play some role in TGF-␤ resistance, 4,13-16 the mechanisms have not yet been well examined.…”

mentioning

confidence: 99%

“…5,10,25,26 We have also reported that Mahlavu cells, an undifferentiated human hepatoma cell line, are resistant to TGF-␤ 1 -mediated growth inhibition and that 12-O-tetradecanoyl phorbol 13-acetate (TPA) could restore TGF-␤ 1 sensitivity. 4 Mahlavu cells, derived from hepatitis B virus-negative African patients, have a sarcomatous, spindle-shaped appearance, 27 whereas they possess the characteristics of hepatocytes such as lipoprotein metabo-lism.…”

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Altered regulation of Src tyrosine kinase by transforming growth factor β1 in a human hepatoma cell line

et al. 1998

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Transforming growth factor βs (TGF‐βs) are the potent growth inhibitors for various cell types. Certain transformed cells, however, show poor response to TGF‐β–induced growth inhibition, which contributes to their uncontrolled proliferation. Recently, we have reported that TGF‐β1 induces degradation of activated Src tyrosine kinase in rat fibroblasts. To elucidate the alteration in TGF‐β signaling pathway in tumor cells that cannot respond to the cytokine, we compared the effects of TGF‐β1 on Src kinase in two human hepatoma cell lines, TGF‐β1–insensitive Mahlavu cells and TGF‐β1–sensitive HepG2 cells. TGF‐β1 decreased Src kinase activity in HepG2 cells, but increased cellular Src levels and Src kinase activity in Mahlavu cells. Co‐incubation of Mahlavu cells with TGF‐β1 and 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA) decreased Src protein levels and Src kinase activity, inducing TGF‐β1sensitivity. TGF‐β1 induced tyrosine dephosphorylation of Ras guanosine triphosphatase–activating protein (Ras‐GAP) and Ras inactivation in HepG2 cells, but induced Ras‐GAP phosphorylation and Ras activation in Mahlavu cells. The Src kinase inhibitor abolished the increase of Src kinase activity in TGF‐β1–treated Mahlavu cells, and induced TGF‐β1 sensitivity. These findings suggest that regulation of Src kinase by TGF‐β1is altered in Mahlavu cells. The altered regulation of Src may contribute to TGF‐β1 insensitivity in this cell line, at least in part through activation of Ras.

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Hepatitis B virus in hepatocarcinogenesis

Feitelson

1999

J. Cell. Physiol.

100

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Hepatitis B virus (HBV) is an important etiologic agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Although the mechanism whereby HBV causes HCC is not fully understood, it is likely that there are many relevant molecular pathways that contribute to the development of HBV-associated HCC. This review provides an overview of some of these proposed pathways and their relative importance. It also raises questions on basic and translational research that will signficantly contribute to the better understanding of underlying mechanisms, prevention, and treatment of this tumor type.

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The Effect of Hepatitis B Virus X Gene Expression on Response to Growth Inhibition by Transforming Growth Factor-β1

Cited by 16 publications

References 0 publications

Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts

Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts

Altered regulation of Src tyrosine kinase by transforming growth factor β1 in a human hepatoma cell line

Hepatitis B virus in hepatocarcinogenesis

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