Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors

• DOI: 10.1007/s13277-012-0555-4
• Publication Date: 2012-12-13T03:49:34Z
• Authors: H. De Vitto; B. S. Mendonça; K. M. Elseth; B. J. Vesper; E. A. Portari; C. V. M. Gallo; W. A. Paradise; F. D. Rumjanek; J. A. Radosevich
• Keywords: 0303 health sciences; Gene Dosage; Breast Neoplasms; NADH Dehydrogenase; DNA, Neoplasm; Nitric Oxide; Adaptation, Physiological; DNA, Mitochondrial; Actins; Mitochondria; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Line, Tumor; Genome, Mitochondrial; Mutation; Breast cancer; mtDNA copy number; NADH dehydrogenase (complex I); Nitric oxide (NO); Somatic mtDNA mutations; Actins; Adaptation, Physiological; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; DNA, Mitochondrial; DNA, Neoplasm; Female; Gene Dosage; Gene Expression Regulation, Neoplastic; Genome, Mitochondrial; Humans; Mitochondria; Mutation; NADH Dehydrogenase; Nitric Oxide; Reactive Oxygen Species; Tumor Suppressor Protein p53; Cancer Research; Humans; Female; Tumor Suppressor Protein p53; Reactive Oxygen Species; Cell Proliferation

Mitochondria combine hydrogen and oxygen to produce heat adenosine triphosphate (ATP). As a toxic by-product of oxidative phosphorylation (OXPHOS), mitochondria generate reactive species (ROS). These free radicals may cause damage mitochondrial DNA (mtDNA) other molecules in the cell. Nitric oxide (NO) plays an important role biology human cancers, including breast cancer; however, it is still unclear how NO might affect genome. The aim current study determine mtDNA oncogenic process. Using sequencing, we studied one cancer cell line as model system investigate effects stress. BT-20 was fully adapted increasing concentrations donor DETA-NONOate referred BT-20-HNO, high (HNO) line. HNO biologically different from "parent" which originated. Moreover, investigated 71 biopsies corresponding noncancerous tissues. radical able somatic mutations BT-20-HNO that were missing parent We identified two mutations, A4767G G13481A, changed amino acid residues. Another point initiation replication site at nucleotide 57 'hot spot' cytidine-rich D300–310 segment. Furthermore, regulated copy number selected populations by clonal expansion. Interestingly, eight coding regions mtDNAs patients (8/71, 11.2 %). All these residues highly conserved potentially leads dysfunctions. displacement loop (D-loop) region [303:315 C(7–8)TC(6) 57] distributed among 14 (14/71, 19.7 Importantly, patients, six had p53 gene. results validate parent/HNO means ROS mtDNA, parallels found subset patient population.