title: Loss of periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced Notch1 activity.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. roshankumar2733@yahoo.com.
authors.forename: Roshan
authors.initials: R
authors.lastname: Sriram
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. vlo101@uottawa.ca.
authors.forename: Vivian
authors.initials: V
authors.lastname: Lo
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. bpryce89@gmail.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pryce
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. l_antonova@hotmail.com.
authors.forename: Lilia
authors.initials: L
authors.lastname: Antonova
authors.affiliation: Children's Hospital of Eastern Ontario, Research Institute, 501 Smyth Road, Ottawa, ON, K1H8L6, Canada. amears@cheo.on.ca.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mears
authors.affiliation: Ottawa Hospital Research Institute, Cancer Therapeutics, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. mdaneshmand@ohri.ca.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Daneshmand
authors.affiliation: Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada. Bruce_McKay@carleton.ca.
authors.forename: Bruce
authors.initials: B
authors.lastname: McKay
authors.affiliation: 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.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Center, McGill University, 1200 Pine Avenue West, Montreal, QC, H3G 1A1, Canada. william.muller@mcgill.ca.
authors.forename: William J
authors.initials: WJ
authors.lastname: Muller
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. lsabourin@ohri.ca.|Ottawa Hospital Research Institute, Cancer Therapeutics, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. lsabourin@ohri.ca.
authors.forename: Luc A
authors.initials: LA
authors.lastname: Sabourin
mesh_terms: D000818:Animals; D001050:Apocrine Glands / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden
chemical_list: D015815:Cell Adhesion Molecules; D018719:Erb-b2 Receptor Tyrosine Kinases; D051881:Receptor, Notch1; D011944:Receptors, Androgen; C512835:POSTN protein, human