Fig. 1

Carbonic anhydrases—particularly, extracellularly localized isoforms—undergo dynamic expression changes during human and murine breast carcinogenesis. A Schematic of how carbonic anhydrases based on their reported expression patterns can accelerate elimination of acidic waste products from solid cancer tissue. Separate cartoons show conditions dominated by oxidative phosphorylation (upper panel) and fermentative glycolysis (lower panel). Cytosol: CA1, CA2, CA3, CA7, and CA13. Mitochondria: CA5α and CA5β. Membrane-associated extracellular-facing: CA4, CA9, CA12, CA14, and CA15. Secreted: CA6. Reactions labeled CA are catalyzed by carbonic anhydrases. Note also the allosteric inhibition of NBCn1 exerted by extracellular H⁺ [23]. MCT, monocarboxylate transporter. The schematic was created with BioRender.com. B + C Transcript levels for carbonic anhydrases in murine ErbB2-induced (B, n = 7–8) and human (C, n = 9–14) breast cancer. Expression levels are reported relative to the reference genes ACTB/Actb and RPS18/Rps18. Data were compared by mixed model analyses followed by Šidák’s post-tests. *P < 0.05, **P < 0.01, ***P < 0.001 vs. normal. N.D., not detectable. D + E Expression of carbonic anhydrases (D) and known hypoxia-responsive gene products (E) in human breast cancer tissue (n = 82–446) of increasing malignancy grade. The data cover the whole breadth of malignant breast tumors without stratification for molecular subtype. Data from the GPL570 platform were extracted from the GENT2 database [38] and compared by one-way ANOVA for trend followed by Holm–Bonferroni adjustment for multiple comparisons. *P < 0.05, **P < 0.01, ***P < 0.001 vs. slope = 0; see Additional file 1: Table S4 for details. We did not evaluate expression of the isoforms CA8, CA10, and CA11 that do no not show carbonic anhydrase catalytic activity