A bi-transgenic murine model of PTTG and PBF overexpression in the thyroid gland

Jim Fong, Martin Read, Gavin Ryan, Gregory Lewy, Vicki Smith, Kristien Boelaert, Jayne Franklyn, Christopher McCabe

Research output: Contribution to journalAbstractpeer-review


Whilst the majority of differentiated thyroid cancers (DTC) have oncogenic mutations, a significant minority may be driven by the overexpression of proto-oncogenes. PTTG and PBF are proto-oncogenes which are induced in DTC, elicit tumours in xenograft models and interact in vitro, where PBF shuttles PTTG into the nucleus. However, the relative contributions of each gene to DTC has not been delineated. Here, we constructed a bi-transgenic murine model over-expressing both PBF and PTTG specifically in the thyroid gland (PTTG/PBF-Tg), and characterised it in comparison to age and sex matched single transgenic (PTTG-Tg, PBF-Tg) and wild-type mice. A total of 68 wild-type, 98 PBF-Tg, 25 PTTG-Tg and 23 PTTG/PBF-Tg mice were assessed. No significant difference in thyroid weight was observed between male and female mice within each of the four genotypes. However, there was a significant 2.7-fold increase in thyroid weight, adjusted for total body weight, in bi-transgenic mice compared to wild-type (P<0.001) at 6 weeks of age. PBF-Tg thyroid weight was 1.7-fold higher than wild-type mice (P<0.001), whereas PTTG thyroid weights were similar to wild-type (0.95-fold; P=0.18). Interestingly, bi-transgenic thyroids were 1.6-fold heavier than PBF-Tg thyroids (P<0.001). Enlarged thyroid growth in bitransgenic mice was accompanied by significant hyperplasia and macrofollicular lesions. As oncogenic expression of PTTG is known to induce genetic instability (GI), we determined GI levels through FISSR-PCR in primary thyroid cultures of each genotype. Compared with WT mice (arbitrary GI index=0%), PBF-Tg mice had a GI index of 19.8±1.8%; PTTG-Tg mice of 7.6±1.6%; and PTTG-Tg/PBF-Tg mice of 37.9±2.7%. Together, our data reveal a complex interplay between PTTG and its binding partner PBF in vivo; the bi-transgenic thyroid phenotype is closer to that of PBF-Tg mice than PTTG-Tg mice, but reveals increased goitre size and heightened genetic instability than either single transgenic model alone.
Original languageEnglish
Article numberOC2.3
JournalEndocrine Abstracts
Publication statusPublished - 2013
EventSociety for Endocrinology BES 2013 - Harrogate, United Kingdom
Duration: 18 Mar 201321 Mar 2013


Dive into the research topics of 'A bi-transgenic murine model of PTTG and PBF overexpression in the thyroid gland'. Together they form a unique fingerprint.

Cite this