ECE2015 Guided Posters Thyroid–genetics (8 abstracts)
Prox1 transcription factor is differentially expressed in thyroid cancer and contributes to the regulation of invasion and migration of thyroid cancer cells
Magdalena Rudzinska 1 , Damian Gawel 1 , Kamila Karpinska 1 , Miroslaw Kiedrowski 2 , Tomasz Stepien 3 , Magdalena Marchlewska 3 , Wanda Krasuska 1 , Joanna Ledwon 1 , Maria Macios 1 , Dariusz Lange 4 & Barbara Czarnocka 1
1Department of Biochemistry and Molecular Biology, The Center of Postgraduate Medical Education, Warsaw, Poland; 2Department of Oncology and Hepatology, Clinical Hospital Ministry of Interior, Warsaw, Poland; 3Department of General and Endocrinological Surgery, Copernicus Memorial Hospital, Warsaw, Poland; 4Department of Tumor Pathology, Institute of Oncology Gliwice Branch, Maria Sklodowska‐Curie Memorial Cancer Center, Gliwice, Poland.
Introduction: The differentiated thyroid cancer (DTC) is the most frequent endocrine malignancy with the incidence increasing worldwide. Although, DTCs are considered to be mostly indolent lesions, the proportion of patients develop metastases. Therefore, identification of molecular factors that are involved in thyroid tumour progression might help to better understand the mechanism of thyroid cancer metastasis. In the present study we examine the role of the transcription factor prospero homeobox 1 (Prox1) in DTC biology. Prox1 is the nuclear transcription factor expressed specifically in LEC cells and as recently shown, also in several human cancers.
Methods: We performed studies using follicular and papillary thyroid cancer derived cell lines. The Prox1 protein and transcript expression levels and its localization were determined using molecular biology methods: Q-RT-PCR, gene silencing, western blot, and immunocytochemistry. To determine the Prox1 role in regulating the hallmarks of malignant cell phenotype we analysed migration, invasion, anchorage-independent growth, proliferation, cell cycle, apoptosis, and adhesion upon Prox1 gene silencing.
Results: We observed significant difference in the Prox1 expression between FTC and PTC derived cancer cell lines. Prox1 transcript and protein levels were overexpressed in follicular cancer cell lines FTC133 and CGTH when compared with PTC cell lines. Moreover, the protein was localized in the nucleus or both the nucleus and cytoplasm respectively. RNA-i knockdown of Prox1 suppressed cellular migration, invasion and anchorage independent growth of FTC-133 cells, whereas proliferation, cell cycle and adhesion were unchanged. Moreover, Prox1 down regulation modified of FTC133 cells shape by actin cytoskeleton reorganization.
Conclusion: Our data suggest an important role for transcription factor Prox1 in i) the regulation of hallmarks of the malignant cell phenotype as migration and invasive capacity and ii) in the actin cytoskeleton remodelling in thyroid cancer cells. Further on-going studies will clarify the role of Prox1 in thyroid cancer cells dissemination.
Volume 37
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Endocrine Abstracts
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