In:
Molecular Carcinogenesis, Wiley, Vol. 56, No. 5 ( 2017-05), p. 1484-1492
Abstract:
PICT‐1 is a nucleolar protein with various tumor suppressor functions. Recently, PICT‐1 expression was reported to be dramatically reduced in several cancers. To investigate the role of PICT‐1 in uterine cervical carcinogenesis, we examined its gene mutations, protein expression, cellular localization, and effect on p53 stabilization. PCR‐SSCP analysis of the entire coding region of PICT‐1 showed that a polymorphism at codon 389 may increase the risk of uterine cervical cancers, and also identified a novel missense mutation. Expression of wild‐type PICT‐1 inhibited the degradation of p53 in the presence or absence of HPV 18 E6 viral protein in vitro , while the expression of codon 389 polymorphic PICT‐1 had a diminished inhibitory effect on p53 degradation. Moreover, we observed that PICT‐1 degradation was induced both independently and cooperatively by E6 and E7 proteins from high‐risk HPVs, but only marginal degradation was observed with proteins from low‐risk HPV. Immunohistochemical staining of tumor samples revealed that lower levels of PICT‐1 were observed in samples from CIN III and cervical cancer tissues, compared to normal cervical epithelium and CIN I, II tissues ( P 〈 0.05). The reduction of PICT‐1 may therefore be an early event in uterine cervical tumorigenesis. Our results indicated that PICT‐1 counteracts HPV‐induced p53 degradation and that aberrant PICT‐1 function may contribute towards inactivating p53. Therefore, PICT‐1 may play a critical role during the pathogenesis of uterine cervical cancers.
Type of Medium:
Online Resource
ISSN:
0899-1987
,
1098-2744
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2001984-1
detail.hit.zdb_id:
1004029-8
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