title: Tyrosine phosphatase PTPα contributes to HER2-evoked breast tumor initiation and maintenance.
abstract: Protein tyrosine phosphatase alpha (PTPα/PTPRA) was shown previously to be overexpressed in human primary breast cancers, and to suppress apoptosis in estrogen receptor-negative breast cancer cells in vitro. However, it is not known whether PTPα is important for mammary tumor initiation, maintenance and/or progression. We have used a combination of three-dimensional cultures, a transgenic mouse model of breast cancer lacking PTPα as well as xenografts of human breast cancer cell lines to address these questions. We found that PTPα knockdown after overt tumor development reduced the growth of HER2-positive human breast cancer cell lines, and that this effect was accompanied by a reduction in AKT phosphorylation. However, PTPα knockdown did not affect invasiveness of HER2-positive human breast cancer cells grown in three-dimensional cultures. Moreover, in MMTV-NeuNT/PTPα(-/-) mice, PTPα ablation did not affect NeuNT-evoked tumor onset or metastasis but decreased the number of tumors per mouse. Thus, we demonstrate that PTPα contributes to both HER2/Neu-mediated mammary tumor initiation and maintenance. Our results suggest that inhibition of PTPα can have a beneficial effect on HER2-positive breast cancers, but that inhibition of additional targets is needed to block breast tumorigenesis.
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: D S
authors: DS
authors: Meyer
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: N
authors: N
authors: Aceto
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: N
authors: N
authors: Sausgruber
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: H
authors: H
authors: Brinkhaus
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: U
authors: U
authors: Müller
authors: Department of Pediatrics and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors: C J
authors: CJ
authors: Pallen
authors: Mechanisms of cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
authors: M
authors: M
authors: Bentires-Alj
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; C516841:PTPRA protein, human; C516843:Ptpra protein, mouse