• Journal of Gastric Cancer
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• 제6권3호
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• pp.181-188
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• 2006

목적: Heregulin은 erbB3와 erbB4의 리간드로 작용한다. 그러나 위암에서 이들 단백의 역할에 대해서는 거의 알려져 있지 않다. 저자들은 위암에서 heregulin과 erbB family 단백 발현 빈도를 알아보고 이들 단백 발현과 임상 병리학적 예후인자와 비교하고자 한다. 대상 및 방법: Tissue microarray와 면역조직화학염색 방법을 이용하여 heregulin과 erbB 단백 발현을 검사하였다. 251 예의 위암을 조기위암, 진행성 위암, 림프절 전이 여부 등에 따라 구분하였다. 결과: Heregulin, erbB1, erbB2, erbB3, erbB4 단백은 각각 64%, 68%, 6%, 88%, 76%로 발현되었다. Heregulin, erbB2, erbB3, erbB4 단백은 장형에서 더 높은 발현을 보였다. Heregulin과 erbB4 단백은 진행성 위암에서 발현이 낮아졌다. ErbB2 단백은 진행성 위암에서 발현이 증가되었다. Heregvlin과 erbB family 단백은 생존율과는 상관관계가 없었다. Heregulin과 erbB3 혹은 heregulin과 erbB4 단백이 동시에 발현되는 군은 장형과 초기 병변에 더 많았다. 결론: Heregulin, erbB3, erbB4 단백들은 주로 위암 초기 병변에 관여하는 것으로 추정된다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.507-513
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• 2000

ErbB3/HER3 is a cell surface receptor which belongs to the ErbB/HER subfamily of receptor protein tyrosine kinases. When expressed in NIH/3T3 cells, ErbB3 can form heterodimeric coreceptor with endogenous ErbB2. Among known intracellular effectors of the ErbB2/ErbB3 are mitogen-activated protein kinase (MAPK) and phosphoinositide (PI) 3-kinase. In the present study, we studied relative contributions of above two distinct signaling pathways to the heregulin-induced mitogenic response via activated ErbB3. For this, clonal NIH-3T3 cell lines expressing wild-type ErbB3 and ErbB3 mutants were stimulated with $heregulin{\beta}_1$. While cyclin D1 level was markedly high and further increased by treatment of heregulin in cells expressing wild-type ErbB3, the elimination of either Shc binding or PI 3-kinase binding lowered both levels. This result was supported by the reduction of cyclin $D_1$ expression by preteatment with MAPK kinase inhibitor or PI 3-kinase inhibitor before stimulation with heregulin. In accordance with the cyclin $D_1$ expression, elimination of either Shc binding or PI 3-kinase binding reduced the heregulin-induced DNA synthesis and cell growth rate. Our results obtained by the comparison of wild-type and ErbB3 mutants indicate that the full induction of the cell cycle progression through $G_1/S$ phase by ErbB3 activation is dependent on both Shc/MAPK and PI 3-kinase signal transduction pathways.

• 한국식품영양과학회지
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• 제32권3호
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• pp.428-436
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• 2003

Carotenoids는 항암 효과가 있는 것으로 알려져 있으나 각각의 carotenoids가 대장암에 미치는 영향에 대해서는 명확하게 밝혀진 바가 없다. 본 연구에서는 4가지 종류의 carotenoids가 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향을 조사하였다. $\alpha$-carotene, $\beta$-carotene, lutein lycopene을 농도를 달리 하여 세포 배양액 에 첨가하여 살아있는 세포의 수를 측정한 결과 $\beta$-carotene는 세포의 증식을 다소 증가시키는 반면 $\alpha$-carotene, lutein, lcopene은 세포의 증식을 감소하였다. 세포의 증식을 억제한 carotenoids 중에서 lycopene이 그 효과가 가장 컸다. ErbB receptor family는 세포의 증식을 촉진하고 대장암에서 그 발현이 증가된 것으로 보고되었기 때문에 lycopene이 heregulin-ErbB3 signaling을 억제하는지를 조사하였다. Lycopene는 ErbB2 단백질을 감소하였고 ErbB3 단백질의 변화를 초래하였다. Heregulin을 첨가하여 인산화를 유도한 경우 ErbB3의 인산화, ErbB3와 p85의 결합, Akt 인산화가 lycopene에 의해 억제되었다. 이 결과들은 carotenoids 중 lycopene이 대장암 세포 증식 억제 효과가 가장 크고, 대장암 세포의 DNA 합성을 억제하고 apoptosis를 유도하는 lycopene효과의 일부는 Erb-B3와 Akt의 인산화 감소에 기인하는 것임을 나타낸다.

• 생명과학회지
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• 제17권3호통권83호
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• pp.356-361
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• 2007

${\beta}-catenin$과 결합하는 ErbB2의 부위를 조사하기 위하여 proteasome에 의하여 분해되지 않는 ${\beta}-catenin$과 다양한 ErbB2 construct를 COS7 세포에 transfection한 후 ErbB2 단백질을 그것의 항체로 가라앉혔다. 이 때 공침한 ${\beta}-catenin$을 Western blot으로 분석하였다. C 말단에서부터 잘려진 ErbB2 단백질 중에 kinase 영역을 가지고 있는 것들만 ${\beta}-catenin$과 공침하였다. kinase 영역의 필요성을 확인하기 위하여 kinase 영역이 내부에서 제거된 ErbB2 construct를 ${\beta}-catenin$과 transfection 한 후 동일한 실험을 실시하였다. 이 실험에서 ${\beta}-catenin$는 kinase 영역이 내부적으로 제거된 ErbB2 단백질과 공침하지 않았다. 이 결과는 ${\beta}-catenin$과 결합하는 ErbB2의 위치는 kinase 영역내에 있음을 제시한다.

• BMB Reports
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• 제43권2호
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• pp.91-96
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• 2010

The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

• 한국식품영양과학회지
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• 제36권8호
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• pp.983-988
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• 2007

본 연구는 녹차의 폴리페놀 성분 중에서 항암효과가 가장 크다고 알려진 EGCG가 인체 유방암 세포 MDA-MB-231의 세포증식억제 기전을 알아보고자 실시하였다. EGCG 처리 농도가 증가할수록 48시간 후에 유방암 세포의 증식이 유의적으로 감소되었다. 세포증식 관련 단백질인 $ErbB_2$, $ErbB_3$, Akt의 단백질 발현은 EGCG의 첨가농도 10 ${\mu}m$ 이상일 때부터 유의적으로 발현이 감소하였고, mRNA 발현은 5 ${\mu}m$ 이상부터 유의적으로 감소되었다. Py20, p-Akt 로 단백질의 인산화를 알아본 결과 EGCG 첨가농도가 증가할수록 $ErbB_2$, $ErbB_3$, Akt 의 인산화가 감소함을 확인할 수 있었다. 본 연구 결과를 종합해 보면 인체 유방암 세포 MDA-MB-231에서 EGCG는 암세포에서 과발현되는 $ErbB_2$, $ErbB_3$, Akt의 세포신호 전달과정 억제를 통하여 암세포의 증식을 억제시키는 것을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.281-286
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• 2008

Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.

• Animal cells and systems
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• 제5권3호
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• pp.247-251
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• 2001

Differentiating HiB5 cells, a rat hippocampal cell line, expressed neuregulins and showed constitutive activation of a neuregulin receptor, ErbB2, suggesting development of a neuregulin autocrine loop. RT-PCR analyses indicated that HiB5 cells produced SMDF and NDF, but not GGF, during the differentiation. None of neuregulin isoforms were detected in proliferating HiB5 cells. The neuregulins in HiBS cells, at least in part, are the $\beta$-isoforms of which the most of neuronal neuregulin isoforms are. The expression of SMDF and NDF was enhanced by PDGF and bFGF that promote cell survival and differentiation, suggesting a close relationship between the synthesis of neuregulins and the differentiation process. HiB5 cells have ErbB2 and ErbB4, but not ErbB3 receptors. Constitutive tyrosine phosphorylation of ErbB2 was detected in HiB5 cells that had not been exposed to exogenous GGF.

• 대한수의학회지
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• 제52권4호
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• pp.269-273
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• 2012

In the present study, we investigated the expression patterns of ErbB family proteins in the pre-pubertal and pubertal mammary glands of dairy cows in association with gland development. For this study, we performed immunohistochemistry for ErbB-1-4 and Ki-67 cell proliferation marker. We found that the pre-pubertal and pubertal mammary glands had typical structures, including ducts and terminal end buds embedded in the stroma, and no development of lobuloalveolar structures. On immunohistochemistry, ErbB-2 and ErbB-3 were strongly expressed in the cytoplasm and nuclei in the epithelial cells of mammary ducts and terminal end buds, and stromal cells, whereas ErbB-1 and ErbB-4 were weakly expressed only in the cytoplasm of gland epithelium and stromal cells, irrespective of the developmental stage. Cell proliferation was inactive in the mammary gland cell compartments in both phases. Thus, expression of the ErbB family in the developing mammary glands was not associated with their functional effects, such as cell proliferation and lobuloalveolar development. In conclusion, ErbB receptors were differentially expressed in the epithelial and stromal cells of virgin mammary glands of dairy cows. Compared with rodent mammary glands, ErbB-3 and ErbB-4 were found to be highly expressed in bovine mammary glands.

• Nutrition Research and Practice
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• 제7권2호
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• pp.89-95
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• 2013

Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol/L$) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of $ErbB_2$ and its active form, $pErbB_2$, were significantly reduced at inorganic sulfur concentrations of 50 ${\mu}mol/L$ and greater than 25 ${\mu}mol/L$, respectively (P < 0.05). The mRNA expression of $ErbB_2$ was significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). The protein expression of $ErbB_3$ and its active form, $pErbB_3$, and the mRNA expression of $pErbB_3$ were significantly reduced at inorganic sulfur concentrations greater than 25 ${\mu}mol/L$ (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.