New insights into the interactions of HPV-16 E6*I and E6*II with p53 isoforms and induction of apoptosis in cancer-derived cell lines.

Autor: Antonio-Véjar V; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, 10450, Mexico; Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, 39090, Guerrero, Mexico; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: 11335@uagro.mx., Ortiz-Sánchez E; Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: eortizs@incan.edu.mx., Rosendo-Chalma P; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, 10450, Mexico; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: peterchalma@hotmail.com., Patiño-Morales CC; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: cpatino@cua.uam.mx., Guido-Jiménez MC; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: mguido@iibiomedicas.unam.mx., Alvarado-Ortiz E; Programa de Posgrado en Ciencias Biológicas. Universidad Nacional Autónoma de México (UNAM), Ciudad de México, 04510, Mexico; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: eduralv.o@gmail.com., Hernández G; Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: ghernandezr@incan.edu.mx., García-Carrancá A; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Ciudad de México, 14080, Mexico. Electronic address: carranca@biomedicas.unam.mx.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2022 Jun; Vol. 234, pp. 153890. Date of Electronic Publication: 2022 Apr 09.
DOI: 10.1016/j.prp.2022.153890
Abstrakt: An important characteristic of cancers associated with high-risk human papillomaviruses (HR-HPV) is the inability of p53 to activate apoptosis due to the effect of the oncoprotein E6. However, the effect of HPV-16 E6 splice variant isoforms (namely E6*I and E6*II), their interaction with the existing p53 isoforms, and their influence on apoptosis is unclear. Here, we report the outcome of ectopic expression of HPV-16 E6, E6*I, and E6*II on the relative levels of p53 and p53 isoforms Δ40p53 and Δ133p53 and their interactions with these proteins. Additionally, we evaluated the effect of ectopic expression of p53, Δ40p53, and Δ133p53 on apoptosis in a p53 null pulmonary cell line (H1299) co-transfected with E6 isoforms and p53 +/+ cell lines with HR-HPV (SiHa and HeLa), transfected with p53 isoforms and treated with cisplatin, a conventional drug used to treat cervical cancer. Our results show that E6 and E6*II induced a significant decrease in p53, but only E6 triggered a Δ40p53 decrease and that E6*II interacts with p53 but not with Δ40p53 and Δ133p53. On the other hand, E6*I did not show any effect or interaction with the p53 isoforms. We found that apoptosis was elevated in H1299 cells transfected with p53 (p = 0.0001) and Δ40p53 (p = 0.0001). A weak apoptotic effect was observed when Δ133p53 was ectopically expressed (p = 0.0195). We observed that both p53 (p = 0.0006) and Δ40p53 (p = 0.0014) induced apoptosis in cisplatin-treated SiHa cells; however in cisplatin-treated HeLa cells, only p53 induced apoptosis (p = 0.0029). No significant differences in apoptosis were observed upon ectopic expression of p53, Δ40p53, and Δ133p53 in SiHa and HeLa cells. Our findings suggest a possible therapeutic application for the combining of p53 or Δ40p53 with cisplatin to induce an increased apoptosis of cancer cells expressing E6 isoforms from HPV-16.
(Copyright © 2022. Published by Elsevier GmbH.)
Databáze: MEDLINE
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