CDH16/Ksp-cadherin is expressed in the developing thyroid gland and is strongly down-regulated in thyroid carcinomas.
Cadherin (CDH)16/kidney-specific-cadherin was first described as a kidney-specific adhesion molecule and thereafter found expressed also in the thyroid gland. We show here that CDH16 fully colocalizes with CDH1/E-cadherin on the basolateral plasma membrane of mouse and human thyrocytes. In thyrocyte cultures, the expression of CDH16 is dependent upon TSH, as other thyroid differentiation markers. In the developing mouse thyroid, CDH16 is expressed at embryonic day 10.5, 1-2 d after the main thyroid-specific transcription factors involved in thyroid cell differentiation. In human thyroid carcinomas, as determined by quantitative RT-PCR, CDH16 expression decreases in papillary, follicular, and anaplastic thyroid carcinomas, and the decrease is more pronounced than that of CDH1. Moreover, by immunofluorescence and confocal microscopy, it appears that although CDH16-negative tumor cells may still be positive for CDH1, CDH1-negative cells are also negative for CDH16, indicating a more extensive loss of the latter and suggesting that CDH16 loss might precede that of CDH1. Loss of CDH16 appears to be a marker of epithelial-mesenchymal transition as indicated by its decrease in cultured thyroid cells after TGF-β treatment. Finally, the decrease in CDH16 is paralleled in part by the decrease in α B-crystallin, which was proposed to mediate the interaction of CDH16 cytosolic tail with the cell cytoskeleton. In conclusion, CDH16 is a thyroid-selective and hormone-dependent adhesion protein that might play a role during thyroid development and that may be a useful marker to monitor thyroid carcinomas.
Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, 80131 Napoli, Italy.
Gaetano
G
Calì
Flaviana
F
Gentile
Sara
S
Mogavero
Pierlorenzo
P
Pallante
Roberto
R
Nitsch
Giuseppe
G
Ciancia
Angelo
A
Ferraro
Alfredo
A
Fusco
Lucio
L
Nitsch
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C513384:CDH1 protein, human; C114483:CDH16 protein, human; C059215:CRYAB protein, human; D015820:Cadherins; D064200:Cdh1 Proteins; C491946:Cdh16 protein, mouse; D018797:Cell Cycle Proteins; D017931:DNA Primers; C577585:Fzr1 protein, mouse; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D038203:alpha-Crystallin B Chain; D013972:Thyrotropin