CDH-16 gene expression in thyroid cell differentiation and transformation.

Objectives: CDH-16/Ksp-cadherin was characterized as a kidney-specific adhesion molecule belonging to the 7-D cadherin family. More recently, alpha B-crystallin was identified as a binding partner of its cytosolic domain and it was suggested to mediate the connection to the actin cytoskeleton. We decided to investigate the expression of CDH-16 in thyroid cells and its potential role in cell differentiation and transformation. Methods: the expression of CDH-16 and alpha B-crystallin in thyroid gland and in thyroid cells was investigated by microarray analysis and by qRT-PCR. Protein localization in the thyroid gland was determined by immunofluorescence and confocal microscopy. TSH-dependent expression of CDH-16 was investigated in rat thyroid cell cultures by qRT-PCR and western blot. CDH-16, E-cadherin and alpha B-crystallin expression in human thyroid tumors was determined by qRT-PCR and by TMA immunofluorescence and confocal microscopy analysis. Results: CDH-16 and alpha B-crystallin were expressed in the thyroid gland, at the basolateral plasma membrane of thyrocytes. CDH-16 was expressed in the mouse thyroid already at E15 and it co-localized with E-cadherin. The expression of CDH-16 in thyroid cell cultures was TSH dependent as most thyroid differentiation markers. In human thyroid tumors CDH-16 and E-cadherin expression was progressively lost. Alpha B-crystallin expression was also markedly decreased. By confocal microscopy, E-cadherin-negative tumor cells were always negative for CDH-16. However, CDH-16-negative cells could be positive for E-cadherin staining. Conclusions: CDH-16 is expressed in the thyroid gland during embryonic development and in the adult, and TSH regulates its expression in thyroid cell cultures. CDH-16, as well as E-cadherin, is lost in thyroid tumors, but the former is the first to be lost during tumor progression. Alpha B-crystallin is also down-regulated in thyroid tumors. Overall these results are suggestive of a role of CDH-16 in thyroid cell differentiation and transformation