In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 41 ( 2005-10-11), p. 14825-14830
Abstract:
Rearrangements of the RET receptor tyrosine kinase gene generating RET / PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET / PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes ( CCL20 , CCL2 , CXCL8 , CXCR4 , L-selectin , GM-CSF , IL1B , MMP9 , UPA , and SPP1 / OPN ) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET / PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET / PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0503039102
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2005
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Bookmarklink