Abstract
Using gene expression profiling, we found that the CBX7 gene was drastically down-regulated in six thyroid carcinoma cell lines versus control cells. The aims of this study were to determine whether CBX7 is related to the thyroid cancer phenotype and to try to identify new tools for the diagnosis and prognosis of thyroid cancer. We thus evaluated CBX7 expression in various snap-frozen and paraffin-embedded thyroid carcinoma tissues of different degrees of malignancy by quantitative reverse transcription-PCR and immunohistochemistry, respectively. CBX7 expression progressively decreased with malignancy grade and neoplasia stage. Indeed, it decreased in an increasing percentage of cases going from benign adenomas to papillary (PTC), follicular, and anaplastic (ATC) thyroid carcinomas. This finding coincides with results obtained in rat and mouse models of thyroid carcinogenesis. CBX7 loss of heterozygosity occurred in 36.8% of PTC and in 68.7% of ATC. Restoration of CBX7 expression in thyroid cancer cells reduced growth rate, with a retention in the G(1) phase of the cell cycle, suggesting that CBX7 can contribute to the proliferation of the transformed thyroid cells. In conclusion, loss of CBX7 expression correlates with a highly malignant phenotype in thyroid cancer patients.
Highlights
Thyroid tumors originating from follicular cells are a good model with which to investigate the events involved in carcinogenesis because they differ in malignant potential from differentiated to undifferentiated phenotypes [1, 2]
To look for genes potentially involved in the neoplastic transformation of the thyroid gland, we extracted RNAs from normal human thyroid primary cells and six human thyroid carcinoma cell lines (WRO cell line from follicular thyroid carcinomas (FTC), TPC-1 and FB-2 cell lines from Papillary thyroid carcinoma (PTC), NPA cell line from a poorly differentiated PTC, and ARO and FRO cell lines from anaplastic carcinomas (ATC)) and hybridized them to U95Av2 Affymetrix oligonucleotide arrays (Affymetrix) containing 12,625 transcripts [14]
We looked for genes whose expression was drastically up- or down-regulated in all the six thyroid carcinoma cell lines versus normal thyroid primary cell culture, on the assumption that genes whose expression was altered in all carcinoma cell lines could be involved in thyroid cell transformation
Summary
Thyroid tumors originating from follicular cells are a good model with which to investigate the events involved in carcinogenesis because they differ in malignant potential from differentiated to undifferentiated phenotypes [1, 2]. In PTC, activation of the RET/PTC oncogene, caused by rearrangements of the RET proto-oncogene, occurs in about 20% of cases [2], whereas the B-RAF gene is mutated in about 40% of cases [4]. These tumors have been associated with TRK gene rearrangements [5] and MET gene overexpression [6]. Critical molecular mechanisms of thyroid carcinogenesis have been clarified, other molecular steps of thyroid neoplastic progression need to be investigated
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