Human epithelial growth factor receptor 2 in human salivary carcinoma ex pleomorphic adenoma: a potential therapeutic target

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Abstract

Background

To inhibit human epithelial growth factor receptor 2 (HER2) in salivary carcinoma ex pleomorphic adenoma (CXPA) and investigate the effects on tumor cell proliferation, cell cycle, and apoptosis. To assess the possibility of blocking HER2 to improve the malignant biological behavior of CXPA.

Materials and methods

HER2 expression and amplification were examined using an immunofluorescence assay and fluorescence in situ hybridization in 2 CXPA cell lines (SM-AP1 and SM-AP4 cells). The effects on tumor cell proliferation, cell cycle, apoptosis, and HER2 downstream pathways were verified after the application of a HER2 inhibitor.

Results

HER2 was overexpressed and amplified in SM-AP1 and SM-AP4 cell lines. After blocking HER2, the tumor proliferation and cell cycle were significantly induced, and the apoptosis process was activated. Moreover, the downstream pathways PI3K/AKT and MAPK/ERK were significantly inhibited.

Conclusion

HER2 was overexpressed and amplified in CXPA cell lines and might thus play an important role in tumor development. Inhibiting HER2 may be a novel targeted therapy for poor biological behavior of CXPA.

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Most cited references 18

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A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.

Edgar R Wood, Anne T Truesdale, Octerloney McDonald … (2004)

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.

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World Health Organization classification of tumours: pathology and genetics of head and neck tumours.

Fabiano Thompson (2006)

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Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population.

Z. Tian, L. Li, L. Wang … (2010)

There is little information in the English-language literature about the epidemiology of salivary gland neoplasms in the eastern Chinese population. A large retrospective study (6982 primary salivary tumors during 23 years) was carried out to investigate the clinicopathological features (tumor location, patient sex and age) of these tumors in this population. 3593 tumors were in males and 3389 in females. Pleomorphic adenoma (69%) was the most common tumor and 20% were located in minor glands. 92% of Warthin's tumors occurred in males. Malignant tumors were predominantly adenoid cystic carcinoma (30%) and mucoepidermoid carcinoma (30%). Incidences of lymphoepithelial carcinomas (5%) and polymorphous low-grade adenocarcinoma (1%) of malignant tumors were identified. 28% of tumors originated from minor glands. Most findings were similar to those in the literature, with some variations. The salivary tumors slightly predominated in males. Relatively higher incidences of minor gland tumors and specifically of pleomorphic adenoma in minor glands were noted. Adenoid cystic carcinoma and mucoepidermoid carcinoma constituted the most common malignancies. There was a high incidence of lymphoepithelial carcinomas but a low incidence of polymorphous low-grade adenocarcinoma. The historical significant male predominance of Warthin's tumor was confirmed.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Manag Res

Journal ID (iso-abbrev): Cancer Manag Res

Journal ID (publisher-id): Cancer Management and Research

Title: Cancer Management and Research

Publisher: Dove Medical Press

ISSN (Electronic): 1179-1322

Publication date Collection: 2018

Publication date (Electronic): 30 November 2018

Volume: 10

Pages: 6571-6579

Affiliations

[1 ]Department of Oral Pathology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, Shanghai 200011, People’s Republic of China, tian0304_cn@ 123456163.com

[2 ]Department of Oral and Cranio-maxillofacial Surgery, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, Shanghai 200011, People’s Republic of China, ywwyww2015@ 123456126.com

Author notes

Correspondence: Zhen Tian, Department of Oral Pathology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, 639 Zhi-zao-ju Road, Shanghai 200011, People’s Republic of China, Tel/Fax +86 21 5331 5687, Email tian0304_cn@ 123456163.com

Wenwen Yu, Department of Oral and Cranio-maxillofacial Surgery, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, 639 Zhi-zao-ju Road, Shanghai 200011, People’s Republic of China, Tel/Fax +86 21 5331 5142, Email ywwyww2015@ 123456126.com

[*]

These authors contributed equally to this work

Article

Publisher ID: cmar-10-6571

DOI: 10.2147/CMAR.S182652

PMC ID: 6280888

PubMed ID: 30555262

SO-VID: 5c7944a5-7c67-4abd-a7be-7ca8e42387e5

License:

The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Human epithelial growth factor receptor 2 in human salivary carcinoma ex pleomorphic adenoma: a potential therapeutic target

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Abstract

Background

Materials and methods

Results

Conclusion

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Karger: Oncology

Most cited references 18

A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.

World Health Organization classification of tumours: pathology and genetics of head and neck tumours.

Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population.

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