Abstract
BackgroundCervical cancer is a major mortality factor in the female population. This neoplastic is an excellent model for studying the mechanisms involved in cancer maintenance, because the Human Papilloma Virus (HPV) is the etiology factor in most cases. With the purpose of characterizing the effects of malignant transformation in cellular activity, proteomic studies constitute a reliable way to monitor the biological alterations induced by this disease. In this contextual scheme, a systemic description that enables the identification of the common events between cell lines of different origins, is required to distinguish the essence of carcinogenesis.ResultsWith this study, we sought to achieve a systemic perspective of the common proteomic profile of six cervical cancer cell lines, both positive and negative for HPV, and which differ from the profile corresponding to the non-tumourgenic cell line, HaCaT. Our objectives were to identify common cellular events participating in cancer maintenance, as well as the establishment of a pipeline to work with proteomic-derived results. We analyzed by means of 2D SDS-PAGE and MALDI-TOF mass spectrometry the protein extracts of six cervical cancer cell lines, from which we identified a consensus of 66 proteins. We call this group of proteins, the "central core of cervical cancer". Starting from this core set of proteins, we acquired a PPI network that pointed, through topological analysis, to some proteins that may well be playing a central role in the neoplastic process, such as 14-3-3ζ. In silico overrepresentation analysis of transcription factors pointed to the overexpression of c-Myc, Max and E2F1 as key transcription factors involved in orchestrating the neoplastic phenotype.ConclusionsOur findings show that there is a "central core of cervical cancer" protein expression pattern, and suggest that 14-3-3ζ is key to determine if the cell proliferates or dies. In addition, our bioinformatics analysis suggests that the neoplastic phenotype is governed by a non-canonical regulatory pathway.
Highlights
Cervical cancer is a major mortality factor in the female population
We see in cervical cancer a unique opportunity to study the malignant transformation because of its common origin: 90.7% of the cases arise as a consequence of High-Risk Human Papilloma Virus (HR-HPV) infection, according to a study carried out in nine countries of diverse cervical cancer incidences [4]
A conserved protein expression pattern exists in cervical cancer cell lines Protein extracts of the six cancer cell lines: two cell lines which are positive for infection with HPV type 18 (HeLa and CaLo), two positive for HPV type 16 (SiHa and CasKi), and two HPV negative (ViBo and C-33A); and HaCaT, a spontaneously immortalized keratinocyte cell line we used as control, were obtained and analyzed by 2D SDS-PAGE (Figure 1)
Summary
Cervical cancer is a major mortality factor in the female population. This neoplastic is an excellent model for studying the mechanisms involved in cancer maintenance, because the Human Papilloma Virus (HPV) is the etiology factor in most cases. With the purpose of characterizing the effects of malignant transformation in cellular activity, proteomic studies constitute a reliable way to monitor the biological alterations induced by this disease In this contextual scheme, a systemic description that enables the identification of the common events between cell lines of different origins, is required to distinguish the essence of carcinogenesis. Among the high-risk types HPV16 and HPV18 are the most prevalent, present in 54.6% and 11% of squamous cervical carcinomas, respectively [4] This is part of the reason why, cervical cancers derived from patients infected with those viral types, have been intensively studied, and one of the best studied human cell line, HeLa, is positive for HPV18 [9]. It is pertinent to mention that there are other cell lines which originated from HPV negative cervical cancers that have been widely studied and enable the visualization of alterations in protein expression, common to many cervical cancer cell lines independently of their origin
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