Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC.

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Emergence of salivary gland cell lineage diversity suggests a role for androgen-independent epidermal growth factor receptor signaling

Journal of Cell Science ◽

10.1242/jcs.108.6.2205 ◽

1995 ◽

Vol 108 (6) ◽

pp. 2205-2212

Author(s):

E.M. Durban ◽

P.G. Nagpala ◽

P.D. Barreto ◽

E. Durban

Keyword(s):

Salivary Gland ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Egf Receptor ◽

Cell Lineage ◽

Mrna Levels ◽

Receptor Signaling ◽

Receptor Mrna ◽

Epidermal Growth ◽

Lineage Diversity

Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor signaling during emergence of cell lineage diversity. Temporal fluctuations in EGF receptor mRNA levels coincident with crucial differentiative cell lineage transitions were revealed by RNase protection analyses. Between days 2 and 5, when proacinar cells are maturing and striated duct cells emerge, EGF receptor mRNA levels were highest and all differentiating cells exhibited EGF receptor immunoreactivity. EGF receptor mRNA levels then declined sharply and immunoreactivity became confined to ductal cells. At day 11 in male mice, and days 11 and 16 in females, a second increase in EGF receptor mRNA was detected coincident with emergence of granular convoluted tubule (GCT) cells. With completion of androgen-dependent GCT cell differentiation at the onset of puberty, EGF receptor mRNA levels and intensity of immunoreactivity decreased. Androgen effects on EGF receptor mRNA or immunoreactivity could not be detected. These temporally distinct patterns of EGF receptor expression suggest that this signaling pathway is a mechanism of potential importance in emergence of cell lineage diversity in a glandular organ.

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