An essential role of maspin in embryogenesis and tumor suppression
Dzinic SH, Bernardo MM, Li X, Fernandez-Valdivia R, Ho Y, Mi Q, Bandyopadhyay S, Lonardo F, Vranic S, Oliveira DS, Bonfil RD, Dyson G, Chen K, Omerovic A, Sheng X, Han X, Wu D, Bi X, Cabaravdic D, Jakupovic U, Wahba M, Pang A, Harajli D, Sakr WA, Sheng S. An essential role of maspin in embryogenesis and tumor suppression. Cancer research 2017; 77(4):886-896.
Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities. Specifically, maspin-deficient mice exhibited pulmonary adenocarcinoma, myoepithelial hyperplasia of the mammary gland, hyperplasia of luminal cells of dorsolateral and anterior prostate, and atrophy of luminal cells of ventral prostate and stratum spinosum of epidermis. These cancer phenotypes were accompanied by increased inflammatory stroma. These mice also displayed the autoimmune disorder alopecia aerate. Overall, our findings defined context-specific tumor suppressor roles for maspin in a clinically relevant model to study maspin functions in cancer and other pathologies.
Medical Subject Headings
Alopecia Areata; Animals; Embryonic Development; Female; Histone Deacetylase 1; Male; Mammary Glands, Animal; Mice; Mice, Inbred C57BL; Organ Specificity; Prostate; Serpins; Tumor Suppressor Proteins