Publications [#214669] of Gayathri R Devi

Papers Published

1. ZI Thomas, W Gibson, JZ Sexton, KM Aird, SM Ingram, A Aldrich, HK Lyerly, GR Devi, KP Williams, Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration., British journal of cancer, vol. 104 no. 10 (May, 2011), pp. 1575-86, ISSN 1532-1827 [doi]
   (last updated on 2013/05/13)

   Abstract:
   BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer with distinct molecular profiles. Gene expression profiling previously identified sonic hedgehog (SHH) as part of a gene signature that is differentially regulated in IBC patients. METHODS: The effects of reducing GLI1 levels on protein expression, cell proliferation, apoptosis and migration were determined by immunoblots, MTT assay, Annexin-V/PI assay and conventional and automated cell migration assays. RESULTS: Evaluation of a panel of breast cancer cell lines revealed elevated GLI1 expression, typically a marker for hedgehog-pathway activation, in a triple-negative, highly invasive IBC cell line, SUM149 and its isogenic-derived counterpart rSUM149 that has acquired resistance to ErbB1/2 targeting strategies. Downregulation of GLI1 expression in SUM149 and rSUM149 by small interfering RNA or a small molecule GLI1 inhibitor resulted in decreased proliferation and increased apoptosis. Further, GLI1 suppression in these cell lines significantly inhibited cell migration as assessed by a wound-healing assay compared with MCF-7, a non-invasive cell line with low GLI1 expression. A novel high-content migration assay allowed us to quantify multiple effects of GLI1 silencing including significant decreases in cell distance travelled and linearity of movement. CONCLUSIONS: Our data reveal a role for GLI1 in IBC cell proliferation, survival and migration, which supports the feasibility of targeting GLI1 as a novel therapeutic strategy for IBC patients.

   Keywords:
   Apoptosis • Cell Growth Processes • Cell Line, Tumor • Cell Movement • Female • Gene Expression Profiling • Humans • Inflammatory Breast Neoplasms • Molecular Targeted Therapy • RNA, Small Interfering • Transcription Factors • administration & dosage • antagonists & inhibitors* • biosynthesis* • drug effects • genetics • metabolism* • methods • pathology • therapy*