Year: 2012
Type: dissertation
Abstract: Various epidemiological studies show that breast cancer is the most common type of cancer in women.Tobacco smoking is associated with increased risk of breast cancer.Polycyclic aromatic hydrocarbons (PAHs) are formed by the incomplete combustion of organic material and are present e.g. in tobacco smoke.Benzo(a)pyrene (BP) is one of the PAHs.BP is metabolized to Benzo(a)pyrene-diol-epoxide (BPDE) which is highly mutagenic and carcinogenic.The aim of this study was to elucidate carcinogenesis related cellular responses induced by BP exposure in breast cancer cell lines and analysing the protective role of p53 protein.Four different human breast cancer cell lines including one with wild type (wt) TP53 gene (ZR-75-1) and three (MDA-MB-231, MDA-MB-486 and T-47-D) with mutant TP53 gene were used for this purpose.Post-translational modifications (e.g.phosphorylations and acetylation) of p53 protein are indicators of activation of p53 protein.Cells were exposed to BP (1µM and 10µM for 48h) in duplicate fashion.The activation of p53 protein in all studied cancer cell lines was compared and evaluated at level of Ser-15 and Ser-392 phosphorylations.Ser-392 phosphorylation was not observed in MDA-MB-231 and T-47-D cell lines after BP exposure.It was found that BP increased phosphorylation of p53 at Ser-392 in ZR-75-1 cells, which have wt p53 protein and in MDA-MB-468 which have mutated p53 protein.Activation of p53 protein by BP is an indication of protective role of p53 against genotoxic insult aiming to protect from carcinogenesis.
Author: Akram, Muhammad
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3097842940