Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis.
BACKGROUND
There are currently no clear markers for the detection of differentiated thyroid cancer and its recurrence. Pituitary tumor transforming gene (PTTG) is a protooncogene implicated in the pathogenesis of multiple tumor types, which stimulates fibroblast growth factor-2 secretion via PTTG binding factor (PBF).


OBJECTIVE
The aim of this study was to ascertain whether PBF expression is associated with thyroid cancer outcome.


METHODS
PBF expression was measured at the mRNA and protein level. Tissue was collected during surgery, with normal samples being taken from the contralateral lobe. In vitro studies ascertained the ability of PBF to transform cells and form tumors in nude mice and its subcellular localization.


METHODS
The study was conducted at a primary care/referral center.


METHODS
Thyroid tumors were collected from a series of 27 patients undergoing surgical excision of papillary and follicular thyroid tumors.


METHODS
No intervention was conducted.


METHODS
The expression of PBF in thyroid cancers compared with normal thyroid, hypothesized before the investigation to be raised in tumors, was the main outcome measure.


RESULTS
PBF mRNA expression was higher in differentiated thyroid carcinomas than in normal thyroid (P < 0.001; n = 27) and was independently associated with tumor recurrence (P = 0.002; R(2) = 0.49). PTTG was able to up-regulate PBF mRNA expression in vitro (P < 0.001; n = 12), and stable overexpression of PBF in NIH3T3 cells resulted in significant colony formation (P < 0.001; n = 12). In vivo, stable sc overexpression of PBF induced tumor formation in athymic nude mice.


CONCLUSIONS
PBF is an additional prognostic indicator in differentiated thyroid cancer that is transforming in vitro and tumorigenic in vivo.
Stratford
Anna L
AL
Division of Medical Sciences, University of Birmingham, Birmingham, B15 2TH, United Kingdom.
Boelaert
Kristien
K
Tannahill
Lesley A
LA
Kim
Dae S
DS
Warfield
Adrian
A
Eggo
Margaret C
MC
Gittoes
Neil J L
NJ
Young
Lawrence S
LS
Franklyn
Jayne A
JA
McCabe
Chris J
CJ
D000328:Adult; D000368:Aged; D000818:Animals; D002471:Cell Transformation, Neoplastic; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology; D009364:Neoplasm Recurrence, Local; D012333:RNA, Messenger / Q000032:analysis; D064249:Securin; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C112633:PTTG1IP protein, human; D012333:RNA, Messenger; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human