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Rev. invest. clín ; 57(3): 434-441, may.-jun. 2005. ilus, tab
Article in Spanish | LILACS | ID: lil-632464

ABSTRACT

High risk human papillomavirus (HPV) infection is considered to be the most important etiological factor of Cervical Uterine Cancer. In order to determine the global expression pattern and to identify possible molecular markers of cervical cancer, cDNA arrays with probe sets complementary to 8,000 human genes were used to examine the expression profiles among 5 cell lines derived from human cervical cancer, three HPV16(+) tumor samples and three normal cervical tissues HPV(-). The levels of expression of different cellular processes were identified. Hierarchical clustering was performed and the gene expression using RT-PCR was confirmed. Two genes were found to be consistently overexpressed in invasive cervical cancer biopsies; one of them, IL-6 was previously reported to be overexpressed in cervical cancer and one novel gene, MMP10, previously not known to be related to cervical cancer. Hierarchical clustering of the expression data revealed that samples with common HPV type infection grouped together, maybe this could mean that differences between HPV types could be indirectly determined by expression profiles.


La infección por virus de papiloma de alto riesgo (VPH) es considerada como el factor etiológico más importante del cáncer cérvico uterino (CaCU). Con el fin de determinar el patrón de expresión global e identificar algunos posibles genes marcadores del CaCU, se utilizaron microhileras de DNA que contenían 8,000 secuencias que codificaban para transcritos diferentes, para estudiar los perfiles de expresión de cinco líneas celulares derivadas de CaCU, tres muestras tumorales conteniendo VPH 16 y tres muestras normales negativas para la presencia de VPH. Se identificaron los niveles de expresión de genes relacionados con diferentes rutas metabólicas. Se llevó a cabo el análisis de agrupamiento jerárquico y posteriormente se confirmó la sobrexpresión de dos genes mediante RT-PCR. Estos dos genes se encontraron sobrexpresados en biopsias tumorales cervicales. Uno de ellos, el gen de IL6, que ha sido previamente reportado en relación con CaCU, así como el gen de la matriz-metaloproteasa 10 (MMP10) por primera vez relacionado con esta neoplasia. El análisis de agrupamiento jerárquico, además, reveló que las muestras que contienen el mismo tipo viral están asociadas, sugiriendo posibles diferencias en expresión entre tipos virales.


Subject(s)
Adult , Female , Humans , Carcinoma, Squamous Cell/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/genetics , Biomarkers, Tumor/genetics , Uterine Cervical Neoplasms/genetics , Biopsy , Colposcopy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Cell Line, Tumor/metabolism , Cell Line, Tumor/virology , Cervix Uteri/pathology , DNA, Complementary/genetics , DNA, Neoplasm/genetics , DNA, Neoplasm/isolation & purification , /biosynthesis , /genetics , Metalloendopeptidases/biosynthesis , Metalloendopeptidases/genetics , Neoplasm Proteins/biosynthesis , Premenopause , Papillomavirus Infections/metabolism , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Biomarkers, Tumor/biosynthesis , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology
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