Transcriptional profile of Ki-Ras-induced transformation of thyroid cells.
In the last years, an increasing number of experiments has provided compelling evidence for a casual role of Ras protein mutations, resulting in their constitutive activation, in thyroid carcinogenesis. However, despite the clear involvement of Ras proteins in thyroid carcinogenesis, the nature of most of the target genes, whose expression is modulated by the Ras-induced signaling pathways and that are ultimately responsible for Ras-induced cellular transformation, remains largely unknown. To analyze Ras-dependent modulation of gene expression in thyroid cells we took advantage of a differentiated rat thyroid cell line, FRTL-5. As a model for Ras-dependent thyroid transformation, we used FRTL-5 cells infected with the Kirsten murine sarcoma virus, carrying the v-Ki-Ras oncogene. The infected cells (FRTL-5 v-Ki-Ras) have lost expression of the thyroid differentiation markers and also are completely transformed. We hybridized two different Affimetrix chips containing probe sets interrogating both known rat genes and ESTs for a total of more than 17,000 sequences using mRNA extracted from FRTL-5 and FRTL-5 v-Ki-Ras cell lines. We identified about 50 genes whose expression was induced and about 40 genes whose expression was downregulated more than 10-fold by Ras. We confirmed the differential expression of many of these genes in FRTL-5 v-Ki-Ras as compared to parental cells by using alternative techniques. Remarkably, we investigated the expression of some of the Ras-regulated genes in human thyroid carcinoma cell lines and tumor samples, our results, therefore, providing a new molecular profile of the genes involved in thyroid neoplastic transformation.
Visconti
Roberta
R
Dipartimento di Biologia e Patologia Cellulare e Molecolare, L. Califano, Universita' degli Studi di Napoli Federico II e/o Istituto di Endocrinologia e Oncologia Sperimentale G. Salvatore del CNR, Napoli, Italy.
Federico
Antonella
A
Coppola
Valeria
V
Pentimalli
Francesca
F
Berlingieri
Maria Teresa
MT
Pallante
Pierlorenzo
P
Kruhoffer
Mogens
M
Orntoft
Torben F
TF
Fusco
Alfredo
A
D000818:Animals; D051927:CD24 Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D011905:Genes, ras; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D013964:Thyroid Neoplasms / Q000235:genetics*
D051927:CD24 Antigen