Induction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells

被引：38

作者：

Akagi, T. ^{[1
,2
]}

Luong, Q. T. ^{[1
,2
]}

Gui, D. ^{[3
]}

Said, J. ^{[2
]}

Selektar, J. ^{[2
]}

Yung, A. ^{[1
]}

Bunce, C. M. ^{[4
]}

Braunstein, G. D. ^{[5
]}

Koeffler, H. P. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Div Hematol & Oncol, Cedars Sinai Med Ctr, Sch Med, Los Angeles, CA 90048 USA

[2] Univ Calif Los Angeles, Samuel Oschin Comprehens Canc Ctr, Cedars Sinai Med Ctr, Sch Med, Los Angeles, CA 90048 USA

[3] Univ Calif Los Angeles, Dept Pathol, Sch Med, Los Angeles, CA 90048 USA

[4] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[5] Univ Calif Los Angeles, Div Endocrinol, Cedars Sinai Med Ctr, Sch Med,Dept Med, Los Angeles, CA 90048 USA

来源：

BRITISH JOURNAL OF CANCER | 2008年 / 99卷 / 05期

关键词：

thyroid cancer; papillary; anaplastic; HNF3; beta/FoxA2; C/EBP beta;

D O I：

10.1038/sj.bjc.6604544

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor ( TSHR). Treatment of thyroid carcinoma cells ( four papillary and two anaplastic cell lines) with histone deacetylase inhibitors ( SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta ( HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein beta (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction ( RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.

引用

页码：781 / 788

页数：8

共 26 条

[1] Nuclear export of phosphorylated C/EBPβ mediates the inhibition of albumin expression by TNF-α [J].

Buck, M ;

Zhang, L ;

Halasz, NA ;

Hunter, T ;

Chojkier, M .

EMBO JOURNAL, 2001, 20 (23) :6712-6723

[2] IODIDE TRANSPORT IN THE THYROID-GLAND [J].

CARRASCO, N .

BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1154 (01) :65-82

[3] Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines - Discussion [J].

Libutti, SK ;

Chun, YS ;

Lo Gerfo, P ;

Clark, OH .

SURGERY, 1998, 124 (06) :1105-1105

[4] Involvement of the PAX8/peroxisome proliferator-activated receptor γ rearrangement in follicular thyroid tumors [J].

Dwight, T ;

Thoppe, SR ;

Foukakis, T ;

Lui, WO ;

Wallin, G ;

Höög, A ;

Frisk, T ;

Larsson, C ;

Zedenius, J .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (09) :4440-4445

[5]

Fagin JA, 1996, CANCER RES, V56, P765

[6] MOLECULAR-BASIS OF THYROID-CANCER [J].

FARID, NR ;

SHI, YF ;

ZOU, MJ .

ENDOCRINE REVIEWS, 1994, 15 (02) :202-232

[7] Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia [J].

Gery, S ;

Gombart, AF ;

Yi, WS ;

Koeffler, C ;

Hofmann, WK ;

Koeffler, HP .

BLOOD, 2005, 106 (08) :2827-2836

[8] A transcriptional profiling study of CCAAT/enhancer binding protein targets identifies hepatocyte nuclear factor 3β as a novel tumor suppressor in lung cancer [J].

Halmos, B ;

Bassères, DS ;

Monti, S ;

D'Aló, F ;

Dayaram, T ;

Ferenczi, K ;

Wouters, BJ ;

Huettner, CS ;

Golub, TR ;

Tenen, DG .

CANCER RESEARCH, 2004, 64 (12) :4137-4147

[9]

Haugen Bryan R., 2004, Current Drug Targets - Immune Endocrine and Metabolic Disorders, V4, P175, DOI 10.2174/1568008043339811

[10] The T/ebp null mouse thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary [J].

Kimura, S ;

Hara, Y ;

Pineau, T ;

FernandezSalguero, P ;

Fox, CH ;

Ward, JM ;

Gonzalez, FJ .

GENES & DEVELOPMENT, 1996, 10 (01) :60-69

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