Relationship between Δ40p53α, Δ133p53α, and p53β/γ isoforms and mitochondrial copy number, with clinical and pathological features in Mexican breast cancer patients

Abstract Expression of WTp53 has been associated with mtDNA copy number (mtDNAcn) in cultured cells and expression of p53 isoforms has been associated with clinical and pathological features of different cancer types, including breast cancer. The objective of this study was to evaluate the relationship between Δ40p53α, Δ133p53α, and p53β/γ isoforms with clinical and pathological features, mitochondrial haplogroups, and mtDNAcn in a Mexican population. Expression of p53 isoforms was evaluated via immunoblot in breast cancer tissue (BCT) and normal adjacent tissue (NAT), to investigate the relationship between protein expression and clinical and pathological features, mitochondrial haplogroups and mtDNAcn. D-loop mtDNA sequencing and real time RT-PCR was performed to determine mtDNA haplogroups and mtDNAcn. Our findings revealed that: (a) expression of Δ40p53α was higher in NAT compared to BCT, (b) expression of Δ133p53α was higher in BCT compared to NAT, and elevated in BCT of patients >50 years old, overweight, and obese; in stage IA; subtypes IDC I-II; ER-positive, PR-positive, HER2-negative, HER3-negative, or luminal A; and mtDNA haplogroups A or B, (c) p53β/γ isoform expression in NAT were higher in patients with haplogroup C, and (d) mtDNAcn was lower in BCT subtype ILC I, stage IIIA, or in BCT of patients with haplogroup C compared to other haplogroups. The differential protein expression of Δ40p53α, Δ133p53α and p53β/γ observed in NAT compared with BCT, containing different clinical and pathological features, and mitochondrial haplogroups may contribute to breast cancer progression and prognosis. These findings have not been reported previously.