title: Expression and functional analysis of Toll-like receptor 4 in human cervical carcinoma.
abstract: Toll-like receptors are expressed in human immune cells and many tumors, but the role of toll-like receptor 4 (TLR4) in the development of tumors is controversial. We demonstrated the expression, distribution, and functional activity of TLR4 in tissues of normal cervix, cervical intraepithelial neoplasia (CIN), invasion cervical cancers (ICC), and different human papillomavirus (HPV)-infected cervical cancer cells. The results showed that TLR4 expression was in accordance with the histopathological grade: higher in ICC than in CIN, and low in normal cervical tissues and malignant cervical stroma. Expression was higher in SiHa (HPV16+) than in HeLa (HPV18+) cells, but was not observed in C33A (HPV-) cells. After treatment with its agonist, lipopolysaccharide (LPS), the expression levels of TLR4 was increased and apoptosis resistance was induced in SiHa cells, but not in HeLa or C33A cells. Meanwhile, LPS treatment did not alter the cell cycle distribution in SiHa cells. The mechanism of apoptosis resistance may be related to HPV16 infection and not correlated with the cell cycle distribution. Targeting TLR4 in combination with traditional drug treatment may serve as a novel strategy for more effectively killing cancer cells.
authors.affiliation: Gynecological Minimal Invasive Center, Beijing Obstetrics Gynecology Hospital, Capital Medical University, Beijing, 100006, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Weng
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Duan
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052162:Human papillomavirus 16; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4