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Volume 10
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10.3390/genes10020127
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Article

Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene

by
Michela Vitiello
1,
Giuseppe Palma
2,
Mario Monaco
3,
Anna Maria Bello
3,
Simona Camorani
1,
Paola Francesca
1,
Domenica Rea
2,
Antonio Barbieri
2,
Gennaro Chiappetta
3,
Gabriella De Vita
4,
Laura Cerchia
1,
Claudio Arra
2,* and
Monica Fedele
1,*
1
Institute of Experimental Endocrinology and Oncology “G. Salvatore” (IEOS), National Research Council (CNR), 80131 Naples, Italy
2
S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori–IRCCS–Fondazione G. Pascale, 80131 Naples, Italy
3
Functional Genomic Unit, Istituto Nazionale Tumori–IRCCS–Fondazione G. Pascale, 80131 Naples, Italy
4
Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Genes 2019, 10(2), 127; https://doi.org/10.3390/genes10020127
Submission received: 14 January 2019 / Revised: 5 February 2019 / Accepted: 5 February 2019 / Published: 9 February 2019
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

PATZ1 is a transcriptional factor downregulated in thyroid cancer whose re-expression in thyroid cancer cells leads to a partial reversion of the malignant phenotype, including the capacity to proliferate, migrate, and undergo epithelial-to-mesenchymal transition. We have recently shown that PATZ1 is specifically downregulated downstream of the Ras oncogenic signaling through miR-29b, and that restoration of PATZ1 in Ha-Ras transformed FRTL5 rat thyroid cells is able to inhibit their capacities to proliferate and migrate in vitro. Here, we analyzed the impact of PATZ1 expression on the in vivo tumorigenesis of these cells. Surprisingly, FRTL5-Ras-PATZ1 cells showed enhanced tumor initiation when engrafted in nude mice, even if their tumor growth rate was reduced compared to that of FRTL5-Ras control cells. To further investigate the cause of the enhanced tumor engraftment of FRTL5-Ras-PATZ1 cells, we analyzed the stem-like potential of these cells through their capacity to grow as thyrospheres. The results showed that restoration of PATZ1 expression in these cells increases stem cell markers’ expression and self-renewal ability of the thyrospheres while limiting their growth capacity. Therefore, we suggest that PATZ1 may play a role in enhancing the stem cell potential of thyroid cancer cells, but, at the same time, it impairs the proliferation of non-stem cells.
Keywords: Ras oncogene; thyroid cancer; thyrospheres; stem cell biology; FRTL5; PATZ1 Ras oncogene; thyroid cancer; thyrospheres; stem cell biology; FRTL5; PATZ1

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MDPI and ACS Style

Vitiello, M.; Palma, G.; Monaco, M.; Bello, A.M.; Camorani, S.; Francesca, P.; Rea, D.; Barbieri, A.; Chiappetta, G.; Vita, G.D.; et al. Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene. Genes 2019, 10, 127. https://doi.org/10.3390/genes10020127

AMA Style

Vitiello M, Palma G, Monaco M, Bello AM, Camorani S, Francesca P, Rea D, Barbieri A, Chiappetta G, Vita GD, et al. Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene. Genes. 2019; 10(2):127. https://doi.org/10.3390/genes10020127

Chicago/Turabian Style

Vitiello, Michela, Giuseppe Palma, Mario Monaco, Anna Maria Bello, Simona Camorani, Paola Francesca, Domenica Rea, Antonio Barbieri, Gennaro Chiappetta, Gabriella De Vita, and et al. 2019. "Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene" Genes 10, no. 2: 127. https://doi.org/10.3390/genes10020127

APA Style

Vitiello, M., Palma, G., Monaco, M., Bello, A. M., Camorani, S., Francesca, P., Rea, D., Barbieri, A., Chiappetta, G., Vita, G. D., Cerchia, L., Arra, C., & Fedele, M. (2019). Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene. Genes, 10(2), 127. https://doi.org/10.3390/genes10020127

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