Functional Analysis of the Cervical Carcinoma Transcriptome: Networks and New Genes Associated to Cancer

Abstract

Cancer is one of the most important public health problem in Mexico and worldwide, especially for female population, breast and cervical cancer (CC) types are the most frequent. Incidence rates of CC are higher in developing countries 40/100,000 women per year vs. 10/100,000 in developed countries (1). In Mexico there are 12,000 new reports cases every year (2). The absence of the screening programs or comparatively ineffective screening programs lead to relatively late diagnosis of the disease and also in differences in the human papillomavirus (HPV) infection (3). Several types of HPV are associated with CC worldwide (4, 5), being the HPV16 the most frequent oncogenic type. Epidemiological and experimental studies suggest that high risk HPV have an important role in cervical carcinogenesis. Persistent viral infection, genetic background in combination with constitutive expression of the viral oncogenes as E6 and E7, are decisive steps for malignant transformation, because these oncoproteins interact with the tumour suppressor proteins p53 and pRB, respectively for their degradation (6, 7). Finally, these interactions could induce cellular proliferation and genetic instability for example, which could promote the accumulation of mutations and aneuploidy (8). In conclusion, viral oncoproteins have a general impact in global profile of expressed genes, which could be analyzed by highthroughput methodologies. One of these techniques is DNA oligonucleotide-based microarray technology, which allows a rapid and high-throughput detection of thousands of transcripts simultaneously (9-11). It has been published several studies about gene expression profiles in HPV infected cells. Mainly these reports are based on gene expression levels altered by E6 and E7 HPV oncoproteins (12-17). Regarding changes in gene expression profiles in cervical cancer