Endocrine Abstracts (2012) 29 OC15.1

PATZ1 is a new candidate tumour-suppressor gene in thyroid cancer

G. Chiappetta2, T. Valentino1, M. Vitiello1, R. Pasquinelli2, M. Monaco2, G. Palma2, C. Arra2, A. Fusco1 & M. Fedele1

1Istituto di Endocrinologia e Oncologia Sperimentale del CNR, Napoli, Italy; 2Istituto dei Tumori di Napoli Fondazione G. Pascale, Napoli, Italy.

Thyroid carcinoma arising from the thyroid follicular epithelium represents the most frequent endocrine malignancy and is mainly associated with gene rearrangements generating RET/PTC and TRK oncogenes, as well as BRAFV600E and RASV12 activating point mutations. Except for p53, which appears to be involved only in poorly differentiated and aggressive histotypes, a role of tumor-suppressor genes in the pathogenesis of thyroid cancer is still poorly known.

We found that the POZ/AT-hook/kruppel Zinc finger 1 (PATZ1) gene is down-regulated, with an inverse correlation to the degree of malignancy and differentiation, in the vast majority of thyroid tumours compared to normal thyroid, suggesting a tumour-suppressor role mainly involved in the late stages of thyroid carcinogenesis.

To explore this possibility, we performed functional studies in the papillary thyroid cancer (PTC)-derived TPC1 and the anaplastic thyroid cancer (ATC)-derived FRO cell lines, in which the expression of PATZ1 is strongly down-regulated with respect to normal thyroid cells. Restoration of PATZ1 expression, by stable DNA transfection, had no effect on the growth rate of both cell lines. Conversely, it led FRO cells to death and highly reduced migratory and invasive capabilities of both cell lines. Finally, we examined the transformed phenotype of the FRO cell transfectants expressing PATZ1, by analyzing their ability to grow in soft agar and to induce tumours in athymic mice. Differently from the parental cell line expressing the empty vector, these transfectants did not form colonies in soft agar and had reduced transforming ability in vivo compared to their controls.

These data indicate that the loss of PATZ1 expression exerts a functional role in the pathogenesis of thyroid cancer, and they are consistent with a specific role of PATZ1 in the signaling pathways involved in cell survival and metastatic progression.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Article tools

My recent searches

No recent searches.