title: An Essential Role ofMaspinin Embryogenesis and Tumor Suppression.
abstract: 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 theMaspingene 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.Cancer Res; 77(4); 886-96. ©2017 AACR.
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Sijana H
authors.initials: SH
authors.lastname: Dzinic
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: M Margarida
authors.initials: MM
authors.lastname: Bernardo
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernandez-Valdivia
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.affiliation: Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Dermatology, Henry Ford Health Systems, Detroit, Michigan.
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.affiliation: Division of Experimental Pathology, Department of Pathology, University Clinical Center, Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.initials: S
authors.lastname: Vranic
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Daniel S M
authors.initials: DS
authors.lastname: Oliveira
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Bonfil
authors.affiliation: Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dyson
authors.affiliation: Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.|Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, Michigan.|Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Almasa
authors.initials: A
authors.lastname: Omerovic
authors.affiliation: Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Peking University Health Science Center, The Third Affiliated Hospital, Beijing, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Dermatology, Henry Ford Health Systems, Detroit, Michigan.
authors.forename: Dinghong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan.|Department of Dermatology, Henry Ford Health Systems, Detroit, Michigan.
authors.forename: Xinling
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Dzenana
authors.initials: D
authors.lastname: Cabaravdic
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Una
authors.initials: U
authors.lastname: Jakupovic
authors.affiliation: Department of Internal Medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, Michigan.
authors.forename: Marian
authors.initials: M
authors.lastname: Wahba
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Aaron
authors.initials: A
authors.lastname: Pang
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Deanna
authors.initials: D
authors.lastname: Harajli
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Wael A
authors.initials: WA
authors.lastname: Sakr
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. ssheng@med.wayne.edu.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.|Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Shijie
authors.initials: S
authors.lastname: Sheng
mesh_terms: D000506:Alopecia Areata / Q000209:etiology; D000818:Animals; D047108:Embryonic Development; D005260:Female; D056284:Histone Deacetylase 1 / Q000502:physiology; D008297:Male; D008321:Mammary Glands, Animal / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011467:Prostate / Q000473:pathology; D015843:Serpins / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C085344:SERPIN-B5; D015843:Serpins; D025521:Tumor Suppressor Proteins; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1