Thesis (M.Sc.) - Cairo University - Faculty of Agriculture - Department of Genetics

In the last years, protein kinase C (PKC) has become an attractive target for the treatment of cancer patients, its widely described role in carcinogenesis and tumor promotion. Despite the extensive research conducted on these phorbol ester receptors there is only limited knowledge about the contribution of each individual PKC isozyme in malignant transformation, mainly due to the different roles of each isozyme and their tissue-specificity. This diversity provides the unique opportunity to develop specific pharmacological agents, but the complex nature of the signaling pathways activated by different PKCs challenges selective drug therapies. Currently, using of Insilico chemistry and molecular modelling for computer-aided drug design has gained significant momentum for the benefit that it is cost effective in research and development of drugs and also it is now standard for finding new drugs worldwide. In this study, we monitored the impact of fever-range hyperthermia on human breast cancer cell line MCF7 considering cell viability and proliferation. MCF7 breast adenocarcinoma cell line was evaluated after exposure to 37{u00B0}C and 40{u00B0}C, cell viability, cell proliferation, and apoptosis were determined. MCF7 showed reduction in the proliferation activity combined with increasing in PKCÜ expression after exposure to fever range hyperthermia. Point mutation was determined using the PKCÜ gene sequence analysis and revealed a missense mutation in the kinase domain converted a conserved hydrophobic amino acid isoleucine into polar threonine that proved its effect on function alternation from suppression to promotion for the proliferation of the MCF7 breast adenocarcinoma cell line. Also, we rationally designed small interfering ribonucleic acid molecules (siRNAs) as it provides a promising therapeutic modality for the treatment of breast cancer

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