CO 005: MOLECULAR MECHANISMS INVOLVED IN THE INHIBITION OF TUMOR CELLS PROLIFERATION EXPOSED TO ELEVATED CONCENTRATIONS OF EPIDERMAL GROWTH FACTOR (EGF)

J Pharm Pharmacogn Res 2(Suppl. 1): S4, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 005: MOLECULAR MECHANISMS INVOLVED IN THE INHIBITION OF TUMOR CELLS PROLIFERATION EXPOSED TO ELEVATED CONCENTRATIONS OF EPIDERMAL GROWTH FACTOR (EGF)

Camacho H, Guillen IA, Berlanga J, Fernández-de-Cossio ME, Pérez L, Palenzuela D, Díaz T, Guillen GE, Herrera L, Cosme K, Gorovaya L, Mendoza O, Fernández JR, Ancizar JA, Suarez J, Tuero A, Ochagavia ME, Roca J, Gavilondo J, García del Barco D, Martin J and Novoa LI.

Center for Genetic Engineering and Biotechnology, CIGB, Havana, Cuba. E-mail: hamlet.camacho@cigb.edu.cu
Abstract

Introduction: The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR.

Material and methods: We used six cancer cell lines (K562, MCF-7, U1906, LS-174T, H125 and A431) with different concentrations of EGFR. An animal model was obtained in Nude mice xenografts with the cell line A431 over-expressing the levels of EGFR The real time PCR technique was used to explore in models in vitro and in vivo, the differential expression of 44 genes involved in EGF signaling pathway and cancer in cells treated with EGF and controls. Relative quantification of gene expression was performed using the software REST 2009 v2.0.13 (QIAGEN GmbH All rights reserved).

Results: The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis.

Conclusions: The inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression.