Abstract 3817: Initial characterization of the prolactin-inducible protein (PIP) null mouse suggests an immunomodulatory role for mPIP

Abstract

Abstract Mouse prolactin-inducible protein (mPIP) is the homologue of the human PIP which is a known marker of both malignant and benign human breast cancer. PIP is shown to be highly expressed and secreted by submandibular, lacrimal and salivary glands. Secreted PIP in saliva has been shown to bind to bacteria suggesting that PIP may play a role in innate host defence. Furthermore, human PIP was shown to be a ligand of the CD4 molecule of T lymphocytes, acting as a potential inhibitor of T cell apoptosis suggesting a role in immune host defence. To address the role of mPIP in innate and adaptive host defence, we generated a PIP knockout mouse (PIP−/−) by targeted gene disruption. Histological as well as physiological and behavioural analyses were used to study the phenotype of these mice. Microarray was also conducted to assess the global effect of mPIP abrogation on gene expression in submandibular glands. PIP−/− mice develop normally with no obvious phenotypic differences that distinguish them from wild-type siblings. However, some adult mutant mice exhibit increased proliferative activity in lymphoid tissues, evident with enlarged submandibular lymph nodes. Light microscopy of these submandibular lymph nodes revealed activated germinal centres with an increased number of immune cells displaying high mitotic and apoptotic rates. Additional analyses showed enlarged medullary regions in the thymus of some PIP−/− mice populated with mature lymphocytes and lymphocytic aggregations within the prostate lobes. As well, analysis of blood cell profiles revealed significant increased in the number of monocytes (p<0.005, n=6) in PIP−/− mice compared to their corresponding littermates. Microarray analysis of gene expression of the submandibular gland of PIP−/− mice also showed differential expression of multiple genes such as Xiap, Dmtf1, Runx1t1, Ccnb2, Notch4, Zeb2 genes which have been shown to be associated with immune disease, cancer and cell survival. In summary our data suggests a role for mPIP in modulation of adaptive and innate immune response in mice. Furthermore, our microarray analysis has revealed novel potential genes and pathways involved in mPIP signalling. (Supported by: Natural Sciences and Engineering Research Council of Canada) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3817.