PMID- 25592291 OWN - NLM STAT- MEDLINE DCOM- 20160115 LR - 20181113 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 17 IP - 1 DP - 2015 Jan 16 TI - Loss of periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced Notch1 activity. PG - 7 LID - 10.1186/s13058-014-0513-8 [doi] LID - 7 AB - INTRODUCTION: Periostin (Postn) is a secreted cell adhesion protein that activates signaling pathways to promote cancer cell survival, angiogenesis, invasion, and metastasis. Interestingly, Postn is frequently overexpressed in numerous human cancers, including breast, lung, colon, pancreatic, and ovarian cancer. METHODS: Using transgenic mice expressing the Neu oncogene in the mammary epithelium crossed into Postn-deficient animals, we have assessed the effect of Postn gene deletion on Neu-driven mammary tumorigenesis. RESULTS: Although Postn is exclusively expressed in the stromal fibroblasts of the mammary gland, Postn deletion does not affect mammary gland outgrowth during development or pregnancy. Furthermore, we find that loss of Postn in the mammary epithelium does not alter breast tumor initiation or growth in mouse mammary tumor virus (MMTV)-Neu expressing mice but results in an apocrine-like tumor phenotype. Surprisingly, we find that tumors derived from Postn-null animals express low levels of Notch protein and Hey1 mRNA but increased expression of androgen receptor (AR) and AR target genes. We show that tumor cells derived from wild-type animals do not proliferate when transplanted in a Postn-null environment but that this growth defect is rescued by the overexpression of active Notch or the AR target gene prolactin-induced protein (PIP/GCDFP-15). CONCLUSIONS: Together our data suggest that loss of Postn in an ErbB2/Neu/HER2 overexpression model results in apocrine-like tumors that activate an AR-dependent pathway. This may have important implications for the treatment of breast cancers involving the therapeutic targeting of periostin or Notch signaling. FAU - Sriram, Roshan AU - Sriram R AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. roshankumar2733@yahoo.com. FAU - Lo, Vivian AU - Lo V AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. vlo101@uottawa.ca. FAU - Pryce, Benjamin AU - Pryce B AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. bpryce89@gmail.com. FAU - Antonova, Lilia AU - Antonova L AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. l_antonova@hotmail.com. FAU - Mears, Alan J AU - Mears AJ AD - Children's Hospital of Eastern Ontario, Research Institute, 501 Smyth Road, Ottawa, ON, K1H8L6, Canada. amears@cheo.on.ca. FAU - Daneshmand, Manijeh AU - Daneshmand M AD - Ottawa Hospital Research Institute, Cancer Therapeutics, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. mdaneshmand@ohri.ca. FAU - McKay, Bruce AU - McKay B AD - Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada. Bruce_McKay@carleton.ca. FAU - Conway, Simon J AU - Conway SJ AD - Developmental Biology and Neonatal Medicine Program, HB Wells Center for Pediatric Research, Indiana University School of Medicine, 705 Riley Hospital Drive, Indianapolis, IN, 46202, USA. siconway@iu.edu. FAU - Muller, William J AU - Muller WJ AD - Department of Biochemistry and Goodman Cancer Research Center, McGill University, 1200 Pine Avenue West, Montreal, QC, H3G 1A1, Canada. william.muller@mcgill.ca. FAU - Sabourin, Luc A AU - Sabourin LA AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. lsabourin@ohri.ca. AD - Ottawa Hospital Research Institute, Cancer Therapeutics, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. lsabourin@ohri.ca. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150116 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Cell Adhesion Molecules) RN - 0 (POSTN protein, human) RN - 0 (Receptor, Notch1) RN - 0 (Receptors, Androgen) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Animals MH - Apocrine Glands/metabolism/pathology MH - Breast Neoplasms/genetics/metabolism/pathology MH - Cell Adhesion Molecules/*deficiency/genetics/metabolism MH - Cell Transformation, Neoplastic/genetics/metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression MH - Genotype MH - Humans MH - Immunohistochemistry MH - Mammary Glands, Animal/metabolism MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Phenotype MH - Receptor, ErbB-2/*genetics/*metabolism MH - Receptor, Notch1/*metabolism MH - Receptors, Androgen/*metabolism MH - Sweat Gland Neoplasms/*genetics/*metabolism/mortality/pathology MH - Tumor Burden PMC - PMC4355979 EDAT- 2015/01/17 06:00 MHDA- 2016/01/16 06:00 PMCR- 2015/01/16 CRDT- 2015/01/17 06:00 PHST- 2014/09/25 00:00 [received] PHST- 2014/12/22 00:00 [accepted] PHST- 2015/01/17 06:00 [entrez] PHST- 2015/01/17 06:00 [pubmed] PHST- 2016/01/16 06:00 [medline] PHST- 2015/01/16 00:00 [pmc-release] AID - s13058-014-0513-8 [pii] AID - 513 [pii] AID - 10.1186/s13058-014-0513-8 [doi] PST - epublish SO - Breast Cancer Res. 2015 Jan 16;17(1):7. doi: 10.1186/s13058-014-0513-8.