MUC4 interacts with ErbB2 in human gallbladder carcinoma: Potential pathobiological implications

Miyahara, Naoki; Shoda, Junichi; Ishige, Kazunori; Kawamoto, Toru; Ueda, Tetsuya; Taki, Ryuuichi; Ohkohchi, Nobuhiro; Hyodo, Ichinosuke; Thomas, Melanie B.; Krishnamurthy, Savitri; Carraway, Kermit L.; Irimura, Tatsuro

doi:10.1016/j.ejca.2008.03.007

Cited by 39 publications

(34 citation statements)

References 21 publications

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“…When all studies were included (regardless of applying ISH for “selected” or “unselected” population), mean HER2 amplification rate was statistically significantly higher in patients with EH-BTCs compared to IHCCs (Table 4). Interestingly, the mean HER2 amplification rate was higher in the five studies [59, 68, 72, 73, 78] in which ISH test was performed in “selected” population when compared to the 12 studies in which ISH test was applied to “unselected population” only [17.9 % (95 % CI 0.1–35.4 %) vs. 57.6 % (95 % CI 16.2–99 %), p value 0.0072] [55, 56, 59, 63, 64, 66, 77, 80–83, 85] (Table 4). Nakazawa et al reported data from 221 patients, 71 of whom had FISH testing performed: meaningful differences in HER2 amplification rate were shown between “unselected” [15/71 (21 %)] and “selected” [15/19 (79 %)] populations [59] (Table 2).…”

Section: Resultsmentioning

confidence: 99%

HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?

Galdy

Lamarca

McNamara

et al. 2016

Cancer Metastasis Rev

147

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Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric cancer, whereas human epidermal growth factor receptor 3 (HER3) is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 overexpression and amplification in biliary tract cancers (BTCs). An electronic search of MEDLINE, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology Congress (ESMO), and American Association for Cancer Research (AACR) was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridization (ISH) in BTCs. Studies were classified as “high quality” (HQ) if IHC overexpression was defined as presence of moderate/strong staining or “low quality” (LQ) where “any” expression was considered positive. Of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5 % (95 % CI 18.9–34.1 %). When HQ studies were analyzed (n = 27 studies), extrahepatic BTCs showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma: 19.9 % (95 % CI 12.8–27.1 %) vs. 4.8 % (95 % CI 0–14.5 %), respectively, p value 0.0049. HER2 amplification rate was higher in patients selected by HER2 overexpression compared to “unselected” patients: 57.6 % (95 % CI 16.2–99 %) vs. 17.9 % (95 % CI 0.1–35.4 %), respectively, p value 0.0072. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9 % (95 % CI 9.7–46.1 %) and 26.5 % (one study), respectively. Up to 20 % of extrahepatic BTCs appear to be HER2 overexpressed; of these, close to 60 % appear to be HER2 amplified, while HER3 is overexpressed or amplified in about 25 % of patients. Clinical relevance for targeted therapy should be tested in prospective clinical trials.

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Section: Resultsmentioning

confidence: 99%

HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?

Galdy

Lamarca

McNamara

et al. 2016

Cancer Metastasis Rev

147

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“…ErbB2 itself has been shown to be significantly overexpressed in human pancreatic ductal adenocarcinomas (45,46) and to regulate inflammatory and cell viability pathways, e.g., by NFκB (47). MUC4 has thus been demonstrated to stimulate proliferation pathways and to inhibit apoptosis induced by chemotherapeutic drugs in different cancer cell lines (27,34,48).…”

Section: Discussionmentioning

confidence: 99%

Mucin production determines sensitivity to bortezomib and gemcitabine in pancreatic cancer cells

Wissniowski¹

2012

Int J Oncol

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Abstract. The prognosis of pancreatic cancer remains disappointing due to a high intrinsic resistance against chemotherapeutic agents. Standard gemcitabine therapies have improved overall survival only marginally and recently, inhibition of the proteasome by the boronic acid derivative bortezomib has been introduced as a novel therapeutic strategy for solid and hematological malignancies including pancreatic cancer. The mucus-producing pancreatic cancer cell line Capan-1 was cultured under standard conditions and treated with different concentrations of gemcitabine or bortezomib. Mucus production was suppressed by siRNA-mediated silencing of apomucin genes. Cell proliferation was determined by 3 H-thymidine incorporation and apoptosis was quantified after propidium iodide staining by flow cytometry. Apoptotic cell death was confirmed by TUNEL staining, determination of mitochondrial transmembrane potential and assessment of caspase 3/7 activity. NFκB-activity was determined by EMSA. The unfolded protein response (UPR) was further investigated by PCR, Western blotting and caspase 12 activity assays. Silencing of MUC4 significantly reduced expression of mucins for up to 5 days after transfection. While native cells showed an increased sensitivity to bortezomib treatment, silenced cells were more sensitive to gemcitabine treatment. Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4. Our data suggest that mucinous pancreatic cancers are more sensitive towards proteasome inhibition by bortezomib and that alternative pathways of apoptosis are involved in cell death induction, while tumor cells with a low secretory activity show a better response to gemcitabine.

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“…11 With its epidermal growth factor (EGF)-like domains, MUC4 acts as a modulator of the human epidermal growth factor receptor 2 (HER2/ErbB2) receptor tyrosine kinase and facilitate tumorigenesis and/or tumor growth in pancreatic carcinoma 12 and gallbladder carcinoma. 13 The prognostic significance of MUC4 expression is tissue-dependent and varies with the type of malignancy. For example, it has been shown that MUC4 expression was related to aggressive tumor behavior or a poor outcome in lung adenocarcinoma, 14 ovarian cancer, 15 and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

Liu

et al. 2016

Medicine

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MUC4 interacts with ErbB2 in human gallbladder carcinoma: Potential pathobiological implications

Cited by 39 publications

References 21 publications

HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?

HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?

Mucin production determines sensitivity to bortezomib and gemcitabine in pancreatic cancer cells

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

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