Τίτλος:
Gene amplification is a relatively frequent event leading to ZBTB7A
(Pokemon) overexpression in non-small cell lung cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
ZBTB7A (Pokemon) is a member of the POK family of transcriptional
repressors. Its main function is the suppression of the p14ARF tumour
suppressor gene. Although ZBTB7A expression has been found to be
increased in various types of lymphoma, there are no reports dealing
with its expression in solid tumours. Given that p14(ARF) inhibits MDM2,
the main negative regulator of p53, we hypothesized that overexpression
of ZBTB7A could lead indirectly to p53 inactivation. To this end, we
examined the status of ZBTB7A and its relationship with tumour kinetics
(proliferation and apoptosis) and nodal members of the p53 network in a
panel of 83 non-small cell lung carcinomas (NSCLCs). We observed, in the
majority of the samples, prominent expression of ZBTB7A in the cancerous
areas compared to negligible presence in the adjacent normal tissue
elements. Gene amplification (two-to five-fold) was found in 27.7% of
the cases, denoting its significance as a mechanism driving ZBTB7A
overproduction in NSCLCs. In the remaining non-amplified group of
carcinomas, analysis of the mRNA and protein expression patterns
suggested that deregulation at the transcriptional and
post-translational level accounts for ZBTB7A overexpression.
Proliferation was associated with ZBTB7A expression (P = 0.033) but not
apoptosis. The association with proliferation was reflected in the
positive correlation between ZBTB7A expression and tumour size (p =
0.018). The overexpression of ZBTB7A in both p53 mutant and p53
wild-type cases, implies either a synergistic effect or that ZBTB7A
exerts its oncogenic properties independently of the p14(ARF)-MDM2-p53
axis. The concomitant expression of ZBTB7A with p14(ARF) (p = 0.039),
instead of the anticipated inverse relation, supports the latter notion.
In conclusion, regardless of the pathway followed, the distinct
expression of ZBTB7A in cancerous areas and the association with
proliferation and tumour size pinpoints a role for this novel cell cycle
regulator in the pathogenesis of lung cancer. Copyright (C) 2007
Pathological Society of Great Britain and Ireland. Published by John
Wiley & Sons, Ltd.
Συγγραφείς:
Apostolopoulou, K.
Pateras, I. S.
Evangelou, K.
Tsantoulis,
P. K.
Liontos, M.
Kittas, C.
Tiniakos, D. G.
Kotsinas,
A.
Cordon-Cardo, C.
Gorgoulis, V. G.
Περιοδικό:
Iranian Journal of Pathology
Λέξεις-κλειδιά:
ZBTB7A; Pokemon; p14(ARF); amplification; overexpression; differential
PCR; lung cancer
