Abstract A28: Bioenergetic analysis of primary human mammary epithelial cells (hMECs)

We have demonstrated reversible suppression of the tumor suppressor protein p53 by respiratory chain deficiency. Further, a recent study from a different group also suggests genetic inactivation of p53 by the impairments of oxidative metabolism, and mutations in mtDNA and TP53 gene coexist in cancers. Therefore, we predict that variation in oxidative metabolism can result in differences in p53 response among individuals. Conditions that suppress oxidative metabolism can impair p53, and thereby promote cancer development. Toward testing this hypothesis, our approach is to quantify the variation in respiratory activity of normal human mammary epithelial cells (hMECs), and then determine the correlation between respiratory activity and p53 response. Thus, we have performed in situ respirometry using 24-well Seahorse Bioscience's Extracellular Flux (XF) Analyzer on hMECs (at passage 2) isolated from breast cancer patients (n=23). The hMECs were isolated from cancer affected (AB) and non-affected (NAB) breasts and differences in parameters affecting mitochondrial bioenergetics under normal and treated (IGF1, TNFα;) conditions were assessed. Our data show 6-9 fold variation in hMECs basal respiratory activity (n=23). Further, 48%, 30% and 22% of patients showed either no difference in mitochondrial respiratory capacity upon addition of pyruvate (-2±5%), or showed at least 10% increase (26±18%) or decrease (-15±3%), respectively. Treatments with selected c...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Metabolic Pathways: Poster Presentations - Proffered Abstracts Source Type: research