The protein interacting with carboxyl terminus-1 codon 389 polymorphism impairs protein interacting with carboxyl terminus-1 function and is a risk factor for uterine cervical cancer.
Mol Carcinog
; 56(5): 1484-1492, 2017 05.
Article
in En
| MEDLINE
| ID: mdl-27996172
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Uterine Cervical Neoplasms
/
Tumor Suppressor Proteins
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2017
Document type:
Article
Affiliation country: