Format

Send to

Choose Destination
Mol Cell Biochem. 2015 Oct;408(1-2):261-72. doi: 10.1007/s11010-015-2504-1. Epub 2015 Jul 15.

Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice.

Author information

1
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Ciudad de México, México.
2
Laboratorio de Biología Molecular del Cáncer, Unidad de Investigación, Hospital Juárez de México, Av. IPN 5160, Magdalena de Las Salinas, Gustavo A. Madero, 07760, Ciudad de México, México.
3
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057-1469, USA.
4
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Ciudad de México, México.
5
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA.
6
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Ciudad de México, México. vidal@cinvestav.mx.

Abstract

Persistent infection with high-risk human papillomaviruses is the main etiological factor in cervical cancer (CC). The human papillomavirus type 16 (HPV16) E7 oncoprotein alters several cellular processes, regulating the expression of many genes in order to avoid cell cycle control. Retinoic acid receptor beta (RARB) blocks cell growth, inducing differentiation and apoptosis. This tumor suppressor gene is gradually silenced in late passages of foreskin keratinocytes immortalized with HPV16 and in various tumors, including CC, mainly by epigenetic modifications. We investigated the effect of E7 oncoprotein on RARB gene expression. We found that HPV16 E7 increases RARB mRNA and RAR-beta protein expression both in vitro and in the cervix of young K14E7 transgenic mice. In E7-expressing cells, RARB overexpression is further increased in the presence of the tumor suppressor p53 (TP53) R273C mutant. This effect does not change when either C33-A or E7-expressing C33-A cell line is treated with Trichostatin A, suggesting that E7 enhances RARB expression independently of histone deacetylases inhibition. These findings indicate that RARB overexpression is part of the early molecular events induced by the E7 oncoprotein.

KEYWORDS:

Cervical cancer; HDACs; HPV16 E7 oncoprotein; RARB; TP53 R273C mutant

PMID:
26173416
DOI:
10.1007/s11010-015-2504-1
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center