title: Down-regulation of leucine zipper putative tumor suppressor 1 is associated with poor prognosis, increased cell motility and invasion, and epithelial-to-mesenchymal transition characteristics in human breast carcinoma.
abstract: Leucine zipper putative tumor suppressor 1 is down-regulated by promoter methylation, but not frequently, in human malignancies, including breast cancer. Recent studies suggest that leucine zipper putative tumor suppressor 1 is a candidate for the metastasis modifier locus on human chromosome 8p in melanoma. In this study, we evaluated whether leucine zipper putative tumor suppressor 1 plays a role in breast cancer metastasis. We found that leucine zipper putative tumor suppressor 1 protein expression was significantly reduced or absent in a series of 340 invasive breast carcinomas compared to normal breast tissue. Lower levels of leucine zipper putative tumor suppressor 1 correlated with high histologic grade, lymph node metastasis, and poor prognosis. Functional studies demonstrated that ectopic expression of leucine zipper putative tumor suppressor 1 in the highly malignant MDA-MB-231 breast cancer cell line suppressed cell proliferation, migration, and invasion in vitro. Expression of leucine zipper putative tumor suppressor 1 in MDA-MB-231 cells also induced a series of changes that are characteristic of mesenchymal-to-epithelial transition, including phenotypic change, up-regulation of epithelial markers E-cadherin, β-catenin, and cytokeratin and down-regulation of the mesenchymal marker vimentin. Expression of leucine zipper putative tumor suppressor 1 also repressed the transcription of Slug and Snail, which both repress E-cadherin expression during epithelial-to-mesenchymal transition. These findings suggest that epithelial-to-mesenchymal transition likely inhibits breast cancer metastasis by intervening in epithelial-to-mesenchymal transition in breast cancer.
authors.affiliation: Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Fu
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D004268:DNA-Binding Proteins; C118711:LZTS1 protein, human; D025521:Tumor Suppressor Proteins