CRTC1 expression during normal and abnormal salivary gland development supports a precursor cell origin for mucoepidermoid cancer

Abstract

Dysregulation of the transcription factor CRTC1 by a t(11;19) chromosomal rearrangement mediates the formation of mucoepidermoid salivary gland carcinoma (MEC). Although the CRTC1 promoter is consistently active in fusion-positive MEC and low levels of CRTC1 transcripts have been reported in normal adult salivary glands, the distribution of CRTC1 protein in the normal salivary gland is not known. The aim of this study was to determine if CRTC1, like many known oncogenes, is expressed during early submandibular salivary gland (SMG) development and re-expressed in an experimental tumor model. Our results indicate that CRTC1 protein is expressed in SMG epithelia during early stages of morphogenesis, disappears with differentiation, and reappears in initial tumor-like pathology. This stage-dependent expression pattern suggests that CRTC1 may play a role during embryonic SMG branching morphogenesis but not for pro-acinar/acinar differentiation, supporting a precursor cell origin for MEC tumorigenesis. Moreover, the coincident expression of CRTC1 protein and cell proliferation markers in tumor-like histopathology suggests that CRTC1-mediated cell proliferation may contribute, in part, to initial tumor formation.