QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.051557v1 306/2/671    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bañuelos, A. Articles by Gariglio, P. Search for Related Content PubMed PubMed Citation Articles by Bañuelos, A. Articles by Gariglio, P.

CELLULAR AND MOLECULAR

Neocarzinostatin Induces an Effective p53-Dependent Response in Human Papillomavirus-Positive Cervical Cancer Cells

Department of Molecular Biomedicine, Escuela Nacional de Medicina y Homeopatía, Instituto Politénico Nacional, Mexico City, Mexico (A.B.); Departments of Morphology and Immunology, Escuela Nacional de Ciencias Biológicas, IPN, Mexico City, Mexico (E.R., M.M.); Department of Genetics and Molecular Biology. Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico (R.O, E.A., P.G.); and Section of Investigation in Cellular Differentiation and Cancer. Laboratory of Immunobiology. Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City, Mexico (A.M.)

Human papillomavirus (HPV) E6 viral oncoprotein plays an important role during cervical carcinogenesis. This oncoprotein binds the tumor suppressor protein p53, leading to its degradation via the ubiquitin-proteasome pathway. Therefore, it is generally assumed that in HPV-positive cancer cells p53 function is completely abolished. Nevertheless, recent findings suggest that p53 activity can be recovered in cells expressing endogenous E6 protein. To investigate whether p53-dependent functions controlling genome integrity, cell proliferation, and apoptosis can be reactivated in cervical cancer cells, we examined the capacity of HeLa, INBL, CaSki, C33A, and ViBo cell lines to respond to neocarzinostatin (NCS), a natural product which induces single- and double-strand breaks in DNA. We found that NCS treatment inhibits cellular proliferation through G₂ cell cycle arrest and apoptosis induction. This effect was preceded by nuclear accumulation of p53 protein and by an increase of p21 transcripts. Although apoptosis was blocked in ViBo cells (HPV-negative), nuclear accumulation of transcriptionally active p53 and inhibition of cell proliferation are observed after NCS treatment. These results suggest that HPV-positive cervical cancer cells are capable of responding efficiently to DNA damage provoked by NCS treatment through a p53-dependent pathway in spite of the presence of E6 protein.

Address correspondence to: Dr. Patricio Gariglio, Department of Genetics and Molecular Biology. Centro de Investigación y de Estudios Avanzados del IPN. Av. IPN 2508. Colonia San Pedro Zacatenco, CP 07360, Mexico City, Mexico. E-mail: vidal{at}lambda.gene.cinvestav.mx

This article has been cited by other articles:

				M. Sandoval, M. Morales, R. Tapia, L. del Carmen Alarcon, M. Sordo, P. Ostrosky-Wegman, A. Ortega, and E. Lopez-Bayghen p53 Response to Arsenic Exposure in Epithelial Cells: Protein Kinase B/Akt Involvement Toxicol. Sci., September 1, 2007; 99(1): 126 - 140. [Abstract] [Full Text] [PDF]