Abstract
WISP-2 mRNA and protein was overexpressed in preneoplastic and cancerous cells of human breast. Statistical analyses show a significant association between WISP-2 expression and estrogen receptor (ER) positivity. In normal breast, the expression was virtually undetected. The studies showed that WISP-2 is an estrogen-induced early response gene in MCF-7 cells and the expression was continuously increased to reach a maximum level at 24 h. The estrogen effect was inhibited by a pure antiestrogen (ICI 182,780). Human mammary epithelial cells, in which WISP-2 expression was undetected or minimally detected, responded to 17beta-estradiol by upregulating the WISP-2 gene after transfection with ER-alpha, providing further evidences that WISP-2 expression is mediated through ER-alpha. Overexpression of WISP-2 mRNA by estrogen may be accomplished by both transcriptional activation and stabilization. MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction. In combination with estradiol, progesterone acted as an antagonist inhibiting the expression of WISP-2 mRNA. Moreover, disruption of WISP-2 signaling in MCF-7 cells by use of antisense oligomers caused a significant reduction in tumor cell proliferation. The results are consistent with the conclusion that WISP-2 expression is a requirement for breast tumor cells proliferation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Blotting, Northern
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Blotting, Western
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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CCN Intercellular Signaling Proteins
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Case-Control Studies
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Cell Division / drug effects
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Dactinomycin / pharmacology
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Estradiol / analogs & derivatives*
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Estradiol / pharmacology
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Estrogen Antagonists / pharmacology
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Estrogens / pharmacology*
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Female
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Fulvestrant
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Gene Expression Regulation, Neoplastic / drug effects*
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Hormone Antagonists / pharmacology
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Humans
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Immunoenzyme Techniques
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In Situ Hybridization
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Intercellular Signaling Peptides and Proteins*
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Male
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Middle Aged
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Mifepristone / pharmacology
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Polymerase Chain Reaction
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Progesterone / pharmacology*
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Estrogen / metabolism
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Receptors, Progesterone / metabolism
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Repressor Proteins
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Tumor Cells, Cultured
Substances
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CCN Intercellular Signaling Proteins
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CCN5 protein, human
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Estrogen Antagonists
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Estrogens
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Hormone Antagonists
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Intercellular Signaling Peptides and Proteins
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Neoplasm Proteins
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Oligodeoxyribonucleotides, Antisense
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Protein Synthesis Inhibitors
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RNA, Messenger
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Receptors, Estrogen
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Receptors, Progesterone
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Repressor Proteins
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Transcription Factors
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Dactinomycin
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Fulvestrant
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Mifepristone
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Progesterone
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Estradiol