Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5).

Meezaman, D; Charles, P; Daskal, E; Polymeropoulos, Mihael H.; Martin, Bruce L.; Rose, Mary C.

doi:10.1016/s0021-9258(18)99965-5

Cited by 200 publications

(15 citation statements)

References 48 publications

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“…[␣- 32 P]UTP and [␣-32 P]dCTP were from Amersham (Arlington Heights, IL). RNasin was obtained from Promega (Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA (10 µg) was separated by 1.2% agarose-formaldehyde gel electrophoresis and transferred by capillary blot to a nylon filter (Nytran Plus) in 1 M ammonium acetate. After ultraviolet cross-linking, the filters were hybridized at 62°C as previously described with 32 P-labeled probes (specific activity Ͼ 10 8 counts • min Ϫ1 •µg Ϫ1 ) for MUC5AC, ␥-actin, or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as previously described (45). Filters were washed twice with 250 ml of 2ϫ saline-sodium citrate (SSC) and 0.1% sodium dodecyl sulfate (SDS) at room temperature for 30 min and then with 250 ml of 0.1ϫ SSC and 0.1% SDS at 62°C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…RNA was isolated by the acid guanidinium thiocyanate-phenol-chloroform method (RNAzol B). 32 P-labeled nascent RNA was purified by Bio-Gel P-30 column chromatography (Biospin columns) and hybridized at 52°C for 36 h to DNA targets (10 µg) immobilized on Nytran filter by ultraviolet cross-linking. DNA targets included plasmids containing MUC5AC cDNA, human ␥-actin cDNA, and, as a negative control, the plasmid pBluescript II SK(Ϫ).…”

Section: Methodsmentioning

confidence: 99%

“…MUC5AC is expressed at greater levels than MUC1 or MUC2 in nasal cells (46), nasal polyp tissue (45), nasal turbinates (7), and primary bronchial epithelium (6). In addition, MUC5AC glycoprotein was recently shown to be a major component of respiratory secretions from a subject with bronchial asthma (32) and normal subjects (42). Therefore, our studies have focused on regulation of MUC5AC gene expression.…”

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confidence: 99%

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Neutrophil elastase increasesMUC5ACmRNA and protein expression in respiratory epithelial cells

Voynow

Young

Wang

et al. 1999

American Journal of Physiology-Lung Cellular and Molecular Phys

216

197

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Chronic neutrophil-predominant inflammation and hypersecretion of mucus are common pathophysiological features of cystic fibrosis, chronic bronchitis, and viral- or pollution-triggered asthma. Neutrophils release elastase, a serine protease, that causes increased mucin production and secretion. The molecular mechanisms of elastase-induced mucin production are unknown. We hypothesized that as part of this mechanism, elastase upregulates expression of a major respiratory mucin gene, MUC5AC. A549, a human lung carcinoma cell line that expresses MUC5AC mRNA and protein, and normal human bronchial epithelial cells in an air-liquid interface culture were stimulated with neutrophil elastase. Neutrophil elastase increased MUC5AC mRNA levels in a time-dependent manner in both cell culture systems. Neutrophil elastase treatment also increased MUC5AC protein levels in A549 cells. The mechanism of MUC5AC gene regulation by elastase was determined in A549 cells. The induction of MUC5AC gene expression required serine protease activity; other classes of proteases had no effect on MUC5AC gene expression. Neutrophil elastase increased MUC5AC mRNA levels by enhancing mRNA stability. This is the first report of mucin gene regulation by this mechanism.

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“…[␣- 32 P]UTP and [␣-32 P]dCTP were from Amersham (Arlington Heights, IL). RNasin was obtained from Promega (Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Neutrophil elastase increasesMUC5ACmRNA and protein expression in respiratory epithelial cells

Voynow

Young

Wang

et al. 1999

American Journal of Physiology-Lung Cellular and Molecular Phys

216

197

View full text Add to dashboard Cite

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“…MUC5AC is a mucin which contains cysteine regions and participates in the formation of extracellular gels (7). It is typically expressed in stomach and respiratory tract (8).…”

Section: Introductionmentioning

confidence: 99%

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

Kim

Azad

Morse

et al. 2020

Clinical Cancer Research

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Purpose: Patients with metastatic colorectal cancer (CRC) refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric monoclonal antibody targeting a variant of MUC5AC with specificity to CRC.Patients and Methods: Single arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue.Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required based on the assumption that ensituximab would improve median overall survival by 7 months using a onesided significance level of 10% and 80% power. Written informed consent was obtained from all patients.Results: Sixty-three patients with advanced, refractory CRC were enrolled and 53 subjects were treated in phase 2 arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment related adverse events at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%) and diarrhea (6%). Serious adverse events at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin and hypoxia. No patients discontinued treatment due to drug related adverse events. Conclusions:Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory CRC.Research.

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Aberrant expression ofMUC5AC andMUC6 gastric mucin genes in colorectal polyps

et al. 1999

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Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5).

Cited by 200 publications

References 48 publications

Neutrophil elastase increasesMUC5ACmRNA and protein expression in respiratory epithelial cells

Neutrophil elastase increasesMUC5ACmRNA and protein expression in respiratory epithelial cells

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

Aberrant expression ofMUC5AC andMUC6 gastric mucin genes in colorectal polyps

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