Open AccessCellular distributions of molecules with altered expression specific to thyroid proliferative lesions developing in a rat thyroid carcinogenesis model
Author(s) -
Woo GyeHyeong,
Takahashi Miwa,
Inoue Kaoru,
Fujimoto Hitoshi,
Igarashi Katsuhide,
Kanno Jun,
Hirose Masao,
Nishikawa Akiyoshi,
Shibutani Makoto
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01094.x
Subject(s) - biology , cell cycle , carcinogenesis , downregulation and upregulation , thyroglobulin , cancer research , gene expression profiling , thyroid , microarray analysis techniques , gene expression , cell , endocrinology , cancer , gene , genetics , biochemistry
To identify differentially regulated molecules related to early and late stages of tumor promotion in a rat two‐stage thyroid carcinogenesis model by an antithyroid agent, sulfadimethoxine, microarray‐based microdissected lesion‐specific gene expression profiling was carried out. Proliferative lesions for profiling were divided into two categories: (i) focal follicular cell hyperplasias (FFCH) and adenomas (Ad) as early lesions; and (ii) carcinomas (Ca) as more advanced. In both cases, gene expression was compared with that in surrounding non‐tumor follicular cells. Characteristically, upregulation of cell cycle‐related genes in FFCH + Ad, downregulation of genes related to tumor suppression and transcription inhibitors of inhibitor of DNA binding (Id) family proteins in Ca, and upregulation of genes related to cell proliferation and tumor progression in common in FFCH + Ad and Ca, were detected. The immunohistochemical distributions of molecules included in the altered expression profiles were further examined. In parallel with microarray data, increased localization of ceruloplasmin, cyclin B1, and cell division cycle 2 homolog A, and decreased localization of poliovirus receptor‐related 3 and Id3 were observed in all types of lesion. Although inconsistent with the microarray data, thyroglobulin immunoreactivity appeared to reduce in Ca. The results thus suggest cell cycling facilitation by induction of M‐phase‐promoting factor consisting of cyclin B1 and cell division cycle 2 homolog A and generation of oxidative responses as evidenced by ceruloplasmin accumulation from an early stage, as well as suppression of cell adhesion involving poliovirus receptor‐related 3 and inhibition of cellular differentiation regulated by Id3. Decrease of thyroglobulin in Ca may reflect dedifferentiation with progression. ( Cancer Sci 2009; 100: 617–625)