title: Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ) in normal mammary epithelial cells and breast tumors.
abstract: The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Chanel E
authors: CE
authors: Smart
authors: Marjan E
authors: ME
authors: Askarian Amiri
authors: Ania
authors: A
authors: Wronski
authors: Marcel E
authors: ME
authors: Dinger
authors: Joanna
authors: J
authors: Crawford
authors: Dmitry A
authors: DA
authors: Ovchinnikov
authors: Ana Cristina
authors: AC
authors: Vargas
authors: Lynne
authors: L
authors: Reid
authors: Peter T
authors: PT
authors: Simpson
authors: Sarah
authors: S
authors: Song
authors: Christiane
authors: C
authors: Wiesner
authors: Juliet D
authors: JD
authors: French
authors: Richa K
authors: RK
authors: Dave
authors: Leonard
authors: L
authors: da Silva
authors: Amy
authors: A
authors: Purdon
authors: Megan
authors: M
authors: Andrew
authors: John S
authors: JS
authors: Mattick
authors: Sunil R
authors: SR
authors: Lakhani
authors: Melissa A
authors: MA
authors: Brown
authors: Stuart
authors: S
authors: Kellie
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D042361:Mammary Glands, Human / Q000201:enzymology* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015201:Meta-Analysis as Topic; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D016372:RNA, Antisense / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C486288:PTPRJ protein, human; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3