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Augmented Serum Amyloid A1/2 Mediated by TNF-induced NF-κB in Human Serous Ovarian Epithelial Tumors
- Source :
- Immune Network
- Publication Year :
- 2017
- Publisher :
- The Korean Association of Immunobiologists, 2017.
-
Abstract
- Tumor necrosis factor-α (TNF) is well known to be involved in the immune system and ovarian inflammation. Ovarian cancer is an inflammation-related malignancy that lacks early screening strategies, resulting in late diagnosis followed by high mortality. Based on our previous data, TNF induced abundant serum amyloid A (SAA), an acute phase protein linked to inflammation, in ovarian granulosal cells. To date, the regulation and expression of SAA in ovarian cancer is not fully elucidated. Here, we investigated the relationship between TNF and SAA by comparing human normal ovarian tissues and serous ovarian tumors. We found that SAA1/2 was significantly expressed in tumor tissues, but no or trace expression levels in normal tissues. TNF was also significantly upregulated in ovarian tumor tissues compared to normal tissues. Moreover, TNF significantly increased SAA1/2 levels in human ovarian cancer cell lines, OVCAR-3 and SKOV-3, in a time-dependent manner. Since the SAA1 promoter contains two nuclear factor (NF)-κB sites, we examined whether TNF regulates SAA1 promoter activity. Deletion analysis revealed that the proximal NF-κB site (-95/-85) played a critical role in regulating TNF-induced SAA1 promoter activity. Within 2 h after intraperitoneal injection of lipopolysaccharide, a product known to stimulate release of TNF, SAA preferably localized to ovarian epithelial cells and the thecal-interstitial layers compared to granulosal cell layers. Based on Gene Expression Omnibus (GEO) database, SAA1/2 and TNF were dominantly expressed in advanced grade ovarian cancer. Taken together, the accumulation of SAA1/2 in ovarian cancer could be mediated by TNF-induced NF-κB activation.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
endocrine system diseases
Tumor necrosis factor
Immunology
Cell
Inflammation
Brief Communication
NF-κB
03 medical and health sciences
Ovarian tumor
Ovarian cancer
Internal medicine
medicine
Immunology and Allergy
Serum amyloid A
business.industry
Acute-phase protein
Serum amyloid A1
medicine.disease
female genital diseases and pregnancy complications
3. Good health
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Endocrinology
Cancer research
Tumor necrosis factor alpha
medicine.symptom
business
Subjects
Details
- ISSN :
- 20926685 and 15982629
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Immune Network
- Accession number :
- edsair.doi.dedup.....6c4d6139e5c8e07b9ee97291aaa6e4a7