Gene identification by cDNA arrays in HPV-positive cervical cancer.
BACKGROUND
One of the most frequent malignancies in women worldwide is carcinoma of the uterine cervix. High-risk human papillomavirus (HPV) infection is considered the most important etiological factor of uterine cervical cancer. Our aim was to identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer by means of cDNA arrays.


METHODS
We used cDNA arrays to examine the expression profiles of six cell lines derived from human cervical cancer, three HPV+ tumor samples and three normal (HPV-) epithelium tissues. Data normalization was performed and the top overexpressed genes were obtained. Hierarchical cluster was performed and, to validate some of the differentially expressed genes between normal and carcinogenic samples, semi-quantitative RT-PCR, in situ hybridization and immunohistochemistry were performed in tissue samples.


RESULTS
Four genes were demonstrated to be consistently overexpressed in invasive cervical cancer biopsies; three novel genes not previously related to cervical cancer: MMP10, Lamc2 and Claudin 1. Moreover, overexpression of IL6 and VEGF was corroborated.


CONCLUSIONS
The identification of characteristic molecular changes in cervical cells by carcinogenesis and HPV infection can lead to a better understanding of cervical cancer. cDNA arrays are beginning to provide new possible molecular markers for prognosis and diagnosis. This technology could eventually help to elucidate the biological differences of the particular mechanisms associated with each different HPV-type infection and those with a poor prognosis.
Vázquez-Ortíz
Guelaguetza
G
Oncogenomics Laboratory, Oncological Diseases Research Unit, Oncology Hospital, 21st Century National Medical Center, Mexico City, Mexico. guelav@yahoo.com
Ciudad
Carlos J
CJ
Piña
Patricia
P
Vazquez
Karla
K
Hidalgo
Alfredo
A
Alatorre
Brenda
B
Garcia
Jose A
JA
Salamanca
Fabio
F
Peralta-Rodriguez
Raul
R
Rangel
Angélica
A
Salcedo
Mauricio
M
D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications; D011897:Random Allocation; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology*