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Original Research

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

Liang Xia1 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, [email protected];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, [email protected]

Yang Wang1 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, [email protected]

Yuhua Hu1 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, [email protected]

Chunye Zhang1 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, [email protected]

Ting Gu1 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, [email protected]

Lizhen Wang1 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, [email protected]

Jiang Li1 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, [email protected]

Wenwen Yu2 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, [email protected]Correspondence[email protected]

Zhen Tian1 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, [email protected]Correspondence[email protected]

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Figures & data

Figure 1 The expression of the HER2 protein in SM-AP1, SM-AP4, and fibroblast cells.

Notes: The HER2 protein was expressed in SM-AP1 and SM-AP4 cells, but not in the fibroblasts. Magnification 400×.

Abbreviation: HER2, human epithelial growth factor receptor 2.

Figure 1 The expression of the HER2 protein in SM-AP1, SM-AP4, and fibroblast cells.Notes: The HER2 protein was expressed in SM-AP1 and SM-AP4 cells, but not in the fibroblasts. Magnification 400×.Abbreviation: HER2, human epithelial growth factor receptor 2.

Figure 2 HER2 amplification was detected in SM-AP1 (A) and SM-AP4 (B) cells, but not in the fibroblasts (C).

Notes: Increased copy numbers (more than six) in cells are shown in A and B. HER2/CEP17 ratio =1 is shown in C. Magnification 1000×.

Abbreviation: HER2, human epithelial growth factor receptor 2.

Figure 2 HER2 amplification was detected in SM-AP1 (A) and SM-AP4 (B) cells, but not in the fibroblasts (C).Notes: Increased copy numbers (more than six) in cells are shown in A and B. HER2/CEP17 ratio =1 is shown in C. Magnification 1000×.Abbreviation: HER2, human epithelial growth factor receptor 2.

Figure 3 The effect of lapatinib on HER2 expression and its downstream pathways in SM-AP1 (A) and SM-AP4 (B) cells.

Notes: (A) p-HER2, AKT, p-AKT, and p-ERK were inhibited by lapatinib in a dose-dependent manner in SM-AP1 cells. (B) p-HER2 was inhibited by lapatinib in a dose-dependent manner, and p-ERK was suppressed significantly when the concentration of lapatinib reached at 1 µM in SM-AP4 cells.

Abbreviations: HER2, human epithelial growth factor receptor 2; p-AKT, phosphorylated AKT; p-ERK, phosphorylated ERK; p-HER2, phosphorylated HER2.

Figure 3 The effect of lapatinib on HER2 expression and its downstream pathways in SM-AP1 (A) and SM-AP4 (B) cells.Notes: (A) p-HER2, AKT, p-AKT, and p-ERK were inhibited by lapatinib in a dose-dependent manner in SM-AP1 cells. (B) p-HER2 was inhibited by lapatinib in a dose-dependent manner, and p-ERK was suppressed significantly when the concentration of lapatinib reached at 1 µM in SM-AP4 cells.Abbreviations: HER2, human epithelial growth factor receptor 2; p-AKT, phosphorylated AKT; p-ERK, phosphorylated ERK; p-HER2, phosphorylated HER2.

Table 1 Cell cycle analysis

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Figure 4 Lapatinib inhibits the activity and proliferation of SM-AP1 (A) and SM-AP4 (B) cells, but not those of normal fibroblasts (C).

Note: *Significant at P<0.001.

Abbreviation: CON, control group.

Figure 4 Lapatinib inhibits the activity and proliferation of SM-AP1 (A) and SM-AP4 (B) cells, but not those of normal fibroblasts (C).Note: *Significant at P<0.001.Abbreviation: CON, control group.

Figure 5 The effect of lapatinib on cell cycle of SM-AP1 and SM-AP4 cells.

Note: (A and B) SM-AP1 cell cycle arrested in the G1 phase after lapatinib treatment; (C and D) SM-AP4 cell cycle arrested in the G1 phase after lapatinib treatment; (E and F) normal fibroblast cell cycle was not affected by lapatinib treatment.

Figure 6 Lapatinib promoted the apoptosis of SM-AP1 (A and B) and SM-AP4 cells (C and D), but not that of normal fibroblasts (E and F). The percentage of apoptotic cells was increased in SM-AP1 cells, whereas the percentage of early apoptotic cells was increased in SM-AP4 cells (G). The apoptosis of fibroblasts was not affected by lapatinib (G).

Note: *Significant at P<0.001.

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

Table 1 Cell cycle analysis

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

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Table 1 Cell cycle analysis

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