title: Cellular distributions of molecules with altered expression specific to thyroid proliferative lesions developing in a rat thyroid carcinogenesis model.
abstract: 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.
authors.affiliation: Division of Pathology, National Institute of Health Science, Setagaya-ku, Tokyo, Japan.
authors.forename: Gye-Hyeong
authors.initials: GH
authors.lastname: Woo
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002570:Ceruloplasmin / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D000075983:Nectins; D009602:Nitrosamines / Q000008:administration & dosage / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013412:Sulfadimethoxine / Q000008:administration & dosage / Q000633:toxicity; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015820:Cadherins; C534701:Ccnb1 protein, rat; D015815:Cell Adhesion Molecules; D019926:Cyclin B; D056744:Cyclin B1; C499848:Id3 protein, rat; D051796:Inhibitor of Differentiation Proteins; D000075983:Nectins; D009602:Nitrosamines; D013412:Sulfadimethoxine; C012457:diisopropanolnitrosamine; D013954:Thyroglobulin; D002570:Ceruloplasmin