Activation of tumor cell proliferation by thyroid hormone in a mouse model of follicular thyroid carcinoma

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.

Download Full-text

Differences in tumor cell proliferation, HLA DR expression and lymphocytic infiltration in various types of thyroid carcinoma

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2002-19991 ◽

2002 ◽

Vol 110 (01) ◽

pp. 27-31 ◽

Cited By ~ 3

Author(s):

E. Lindhorst ◽

P.-M. Schumm-Draeger ◽

J. Bojunga ◽

K.-H. Usadel ◽

G. Herrmann

Keyword(s):

Cell Proliferation ◽

Thyroid Carcinoma ◽

Tumor Cell ◽

Lymphocytic Infiltration ◽

Tumor Cell Proliferation ◽

Hla Dr

Download Full-text

Mathematical Modeling of Tumor Cell Proliferation Kinetics and Label Retention in a Mouse Model of Lung Cancer

Cancer Research ◽

10.1158/0008-5472.can-12-4244 ◽

2013 ◽

Vol 73 (12) ◽

pp. 3525-3533 ◽

Cited By ~ 6

Author(s):

Yanyan Zheng ◽

Helen Moore ◽

Alexandra Piryatinska ◽

Trinidad Solis ◽

E. Alejandro Sweet-Cordero

Keyword(s):

Mathematical Modeling ◽

Lung Cancer ◽

Cell Proliferation ◽

Mouse Model ◽

Tumor Cell ◽

Tumor Cell Proliferation ◽

Proliferation Kinetics

Download Full-text

Thyroid hormone receptors are tumor suppressors in a mouse model of metastatic follicular thyroid carcinoma

Oncogene ◽

10.1038/onc.2009.476 ◽

2010 ◽

Vol 29 (13) ◽

pp. 1909-1919 ◽

Cited By ~ 33

Author(s):

X-G Zhu ◽

L Zhao ◽

M C Willingham ◽

S-Y Cheng

Keyword(s):

Thyroid Hormone ◽

Mouse Model ◽

Thyroid Carcinoma ◽

Tumor Suppressors ◽

Hormone Receptors ◽

Follicular Thyroid Carcinoma ◽

Thyroid Hormone Receptors

Download Full-text

Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

BMC Cancer ◽

10.1186/1471-2407-13-251 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 33

Author(s):

Tao Hu ◽

Chunhua Zhang ◽

Qiongling Tang ◽

Yanan Su ◽

Bo Li ◽

...

Keyword(s):

Cell Proliferation ◽

Mouse Model ◽

Tumor Cell ◽

Human Melanoma ◽

Tumor Cell Proliferation ◽

Xenograft Mouse Model ◽

Promote Tumor Cell ◽

Human Melanoma Xenograft ◽

Melanoma Xenograft

Download Full-text

Growth Activation Alone Is Not Sufficient to Cause Metastatic Thyroid Cancer in a Mouse Model of Follicular Thyroid Carcinoma

Endocrinology ◽

10.1210/en.2009-1017 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1929-1939 ◽

Cited By ~ 41

Author(s):

Changxue Lu ◽

Li Zhao ◽

Hao Ying ◽

Mark C. Willingham ◽

Sheue-yann Cheng

Keyword(s):

Thyroid Hormone ◽

Mouse Model ◽

Thyroid Carcinoma ◽

Focal Adhesion ◽

Follicular Thyroid Carcinoma ◽

Gene Knockout ◽

Metastatic Cancer ◽

Genetic Alterations ◽

Human Thyroid ◽

Migration And Invasion

TSH is the major stimulator of thyrocyte proliferation, but its role in thyroid carcinogenesis remains unclear. To address this question, we used a mouse model of follicular thyroid carcinoma (FTC) (TRβPV/PV mice). These mice, harboring a dominantly negative mutation (PV) of the thyroid hormone-β receptor (TRβ), exhibit increased serum thyroid hormone and elevated TSH. To eliminate TSH growth-stimulating effect, TRβPV/PV mice were crossed with TSH receptor gene knockout (TSHR−/−) mice. Wild-type siblings of TRβPV/PV mice were treated with an antithyroid agent, propylthiouracil, to elevate serum TSH for evaluating long-term TSH effect (WT-PTU mice). Thyroids from TRβPV/PVTSHR−/− showed impaired growth with no occurrence of FTC. Both WT-PTU and TRβPV/PV mice displayed enlarged thyroids, but only TRβPV/PV mice developed metastatic FTC. Molecular analyses indicate that PV acted, via multiple mechanisms, to activate the integrins-Src-focal adhesion kinase-p38 MAPK pathway and affect cytoskeletal restructuring to increase tumor cell migration and invasion. Thus, growth stimulated by TSH is a prerequisite but not sufficient for metastatic cancer to occur. Additional genetic alterations (such as PV), destined to alter focal adhesion and migration capacities, are required to empower hyperplastic follicular cells to invade and metastasize. These in vivo findings provide new insights in understanding carcinogenesis of the human thyroid.

Download Full-text

Effect of green tea polyphenol on changes in cancer-related factors in a mouse model of bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.329 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 329-329

Author(s):

Tomohiro Matsuo ◽

Yasuyoshi Miyata ◽

Yuichiro Nakamura ◽

Yasuda Takuji ◽

Akihiro Asai ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Mouse Model ◽

Tumor Cell ◽

Green Tea ◽

Tumor Cell Proliferation ◽

Tea Polyphenol ◽

Green Tea Polyphenol ◽

Anti Cancer ◽

Cox 2

329 Background: Many studies have demonstrated the anti-cancer effects of green tea polyphenol (GTP) in a variety of malignancies including bladder cancer, and epidemiologic studies have shown that green tea consumption reduces cancer risk. New cancer treatment strategies in combination with GTP intake have been recommended for several types of cancer. Thus, GTP is thought to be useful not only for cancer prevention but also for treatment. However, the mechanistic basis of these effects is not well understood. Hence, The aims of this study is to clarify the molecular mechanisms of GTP-induced anti-cancer effects, we used a mouse model of chemically induced bladder cancer. Methods: C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14–24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation, and microvessel density were evaluated along with immunohistochemical analysis of human antigen R (HuR), vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Results: Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. In regard to nuclear HuR, its expression was not associated with any parameters, such as carcinogenesis, muscle invasion, and GTP intake. Conclusions: Our results supported the opinion that GTP intake can suppress tumor progression and malignant behavior in animal model of bladder cancer. In addition, we speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer tissue.

Download Full-text