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

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 localizati...

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Bibliographic Details
Published in:Molecular carcinogenesis 2017-05, Vol.56 (5), p.1484-1492
Main Authors: Yoshimoto, Masafumi, Tokuda, Aoi, Nishiwaki, Kunihiko, Sengoku, Kazuo, Yaginuma, Yuji
Format: Article
Language:English
Subjects:
carcinogenesis
Cell Line, Tumor
Cervical cancer
Codon
DNA-Binding Proteins - metabolism
Female
Genetic Predisposition to Disease
HeLa Cells - virology
Human papillomavirus
Human papillomavirus 18 - pathogenicity
Humans
Middle Aged
Mutation
Oncogene Proteins, Viral - metabolism
Papillomaviridae
PICT‐1
polymorphism
Polymorphism, Genetic
Protein Stability
Proteins
risk factor
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
uterine cervical cancer
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - virology
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Summary: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 
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22608