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

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

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

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6789-6794
• /
• 2015

Background: To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Materials and Methods: Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. Results: The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Conclusions: Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

• 대한임상검사과학회지
• /
• 제36권2호
• /
• pp.185-192
• /
• 2004

Overexpressions of the estrogen receptors(ER), progesterone receptors(PR) and C-erbB-2 protein are important determiners of the response to chemotherapy in the breast cancer. For detecting ER, PR and C-erbB-2, immunohistochemistry are currently regarded as standard method. The purposes of this study compared to histologic grade and expression of the ER, PR and C-erbB-2 in breast cancer. We examined overexpression of ER, PR and C-erbB-2 protein in 84 breast carcinomas by using immunohistochemical stains. The following results were obtained. For histologic grade, 10 cases(11.9%) showed carcinoma in situ, 16 cases(19%) showed grade I, 36 cases (42.9%) showed grade II, and 22 cases(26.2%) showed grade III among the 84 test samples. The average positive rate ER and PR was 63%, 46% showed carcinoma in situ, 80%, 60% showed grade I, 64%, 41% showed grade II, 34%, 23% showed grade III, respectively. The induction of PR increased when induction of ER increased, thus showing significant relationship(p<0.05). The expression of C-erbB-2 protein was 9 cases(10.7%) in one positive(1+), 9 cases(10.7%) in two positive(2+), and 9 cases(10.7%) in three positive(3+). C-erbB-2 protein expression showed no statistical significance. In conclusion, ER and PR positive rates were inversely associated with histologic grades significantly(p<0.05). C-erbB-2 showed no significant difference with histologic grade. However ER, PR and C-erbB-2 showed significant relationship with each other(p<0.05). Therefore, these findings might be an important prognostic factor and might be arranged as a regular pathological examination in cases of breast cancer.

• 한국동물학회:학술대회논문집
• /
• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
• /
• pp.233.2-233
• /
• 1998

No Abstract, See Full Text

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5709-5714
• /
• 2014

Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of $58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study.

• 미생물학회지
• /
• 제47권1호
• /
• pp.1-6
• /
• 2011

암의 유전자치료에서 암세포로의 선택적 유전자전달 매체의 부족은 치료효과의 감소를 야기하는 문제이다. 본 연구에서는 난소암 유전자치료의 효율을 높이기 위한 목적으로 난소암세포로 선택적인 유전자전달을 하도록 개량된 아데노바이러스 벡터를 제조하고, 그 효율성을 난소암세포주를 이용하여 조사하였다. 난소암세포에 과다발현하는 분자인 ErbB receptor를 표적하도록 아데노바이러스 외피단백질 fiber에 ErbB receptor에 대한 ligand인 heregulin으로부터 유래한 펩티드를 부착하였다. 53개의 아미노산으로 구성된 외부 펩티드를 fiber에 부착하였을 때 바이러스 감염에 중요한 기능을 하는 fiber 삼량체 구조 형성에 영향을 미치지 않았다. Fiber를 조작한 개량 아데노바이러스는 야생형 fiber를 가진 1세대 아데노바이러스 벡터에 비해 선택적으로 난소암으로 유전자를 전달하는 비율이 증가하였다. 특히 항암제에 저항성을 가진 난소암세포주 OVCAR3에서 유전자전달 효율이 약 5배 증가되었다. 따라서 난소암의 유전자치료에서 개량된 아데노바이러스로 치료 유전자를 전달하면 치료의 효율성을 향상시킬 수 있을 것이다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3857-3862
• /
• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Molecules and Cells
• /
• 제43권1호
• /
• pp.34-47
• /
• 2020

The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo. Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.