Decreased expression of retinoid X receptor isoforms in human thyroid carcinomas.
Retinoid X receptors (RXRs) are ligand-inducible transcription factors that belong to the superfamily of nuclear hormone receptors. Because RXRs heterodimerize with thyroid hormone receptor, retinoic acid receptor, vitamin D(3) receptor, and peroxisome proliferator-activated receptor, they play central roles in regulating a number of signaling pathways. To understand the roles of RXRs in human thyroid carcinogenesis, we have investigated the immunohistochemical expression of RXRs in normal and neoplastic thyroid tissues. Whereas nontumorous human thyroid cells exhibited distinct nuclear staining for the RXRs, thyroid carcinomas showed decreased nuclear expression of all three RXR isoforms. In particular, some thyroid carcinoma cells showed intense RXR-alpha cytoplasmic staining accompanied by decreased immunoreactivity in their nuclei. This subcellular localization of RXR-alpha was confirmed by Western blot analysis, which showed both lower nuclear expression levels of RXR-alpha and a cytosolic presence of RXR-related protein in neoplastic regions. We present here, for the first time, the histological distribution of each RXR protein (alpha, beta, and gamma) in human thyroid follicular cells. In addition, we found that the nuclear expression of RXRs was lower in thyroid carcinomas than in normal tissue. The differential expressions of these RXRs in thyroid carcinomas might be implicated in the pathogenesis of thyroid cancers.
Takiyama
Yumi
Y
The Second Department of Internal Medicine, School of Medicine, Asahikawa Medical College, Midorigaoka higashi 2-1-1-1, Asahikawa 078-8510, Japan. taka0716@asahikawa-med.ac.jp.
Miyokawa
Naoyuki
N
Sugawara
Akira
A
Kato
Shizuo
S
Ito
Koichi
K
Sato
Keisuke
K
Oikawa
Kensuke
K
Kobayashi
Hiroya
H
Kimura
Shoji
S
Tateno
Masatoshi
M
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008970:Molecular Weight; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D047488:Retinoid X Receptors / Q000032:analysis* / Q000235:genetics; D013961:Thyroid Gland / Q000737:chemistry; D013964:Thyroid Neoplasms / Q000737:chemistry*
D020033:Protein Isoforms; D012333:RNA, Messenger; D047488:Retinoid X Receptors