Molecular and Cellular Pathobiology An Essential Role ofMaspin in Embryogenesis and Tumor Suppression
نویسندگان
چکیده
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. Cancer Res; 77(4); 886–96. 2017 AACR.
منابع مشابه
Bacterial and tissue biomarkers of gastric cancer: new findings and future perspectives: review article
Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. It has been proposed that the specific genotypes of Helicobacter pylori (H. pylori) are the causative agents in the development of gastroduodenal diseases, such as chronic atrophic gastritis, peptic ulcerations, and GC. However, disease progression to GC occurs in only a small proportion of infected patients. Re...
متن کاملDown-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines
Objective(s): The OCT4B1, as one of OCT4 variants, is expressed in cancer cell lines and tissues more than other variants and plays an important role in apoptosis and stress (heat shock protein) pathways. The present study was designed to determine the effects of OCT4B1 silencing on expressional profile of HSP40 gene family expression in three different human tumor cell lines. Materials and Met...
متن کاملDecreased Liver Tissue Wasting following High-Intensity Interval Training through Apoptosis Signaling Suppression in Breast Tumor–Bearing Female Mice
Introduction: Cachexia is a cancer complication that is associated with increased weight loss. Apoptosis has been known as one of the tissue-wasting pathways that cause weight loss and multiple organ failure in cancer-related cachexia. Various factors, including exercise training, can be effective in the reduction of cancer cachexia. In the present study, the effect of four weeks of high-intens...
متن کاملThe emerging role of senescent cells in tissue homeostasis and pathophysiology
Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remod...
متن کاملThe Relationship between the Expression of Small Heat-Shock Proteins and Suppression of OCT4B1
Background: OCT4B1, a variant of OCT4, is expressed in both cancer cells and tissues. This variant has a main role in the regulation of both apoptotic and stress (heat-shock proteins) pathways. The aim of this study was to investigate the effects of OCT4B1 silencing on the expression of small heat-shock proteins (sHSPs)in three human tumor cell lines. Methods:...
متن کامل