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Cellular Distributions of Molecules with Altered Expression Specific to Thyroid Proliferative Lesions Developing in a Rat Thyroid Carcinogenesis Model

Overview
Journal Cancer Sci
Specialty Oncology
Date 2009 Mar 21
PMID 19298605
Citations 1
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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.

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References
1.
Yamamoto H, Monden T, Ikeda K, Izawa H, Fukuda K, Fukunaga M . Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer. Br J Cancer. 1995; 71(6):1231-6. PMC: 2033831. DOI: 10.1038/bjc.1995.238. View

2.
Draetta G, Luca F, Westendorf J, Brizuela L, Ruderman J, Beach D . Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell. 1989; 56(5):829-38. DOI: 10.1016/0092-8674(89)90687-9. View

3.
Smith P, Williams E, Wynford-Thomas D . In vitro demonstration of a TSH-specific growth desensitising mechanism in rat thyroid epithelium. Mol Cell Endocrinol. 1987; 51(1-2):51-8. DOI: 10.1016/0303-7207(87)90118-3. View

4.
Hough C, Cho K, Zonderman A, Schwartz D, Morin P . Coordinately up-regulated genes in ovarian cancer. Cancer Res. 2001; 61(10):3869-76. View

5.
Imai T, Onose J, Hasumura M, Ueda M, Takizawa T, Hirose M . Sequential analysis of development of invasive thyroid follicular cell carcinomas in inflamed capsular regions of rats treated with sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation. Toxicol Pathol. 2004; 32(2):229-36. DOI: 10.1080/01926230490274380. View