title: WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation.
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.
authors.affiliation: Cancer Research Unit, Research Division, V.A. Medical Center, Kansas City, MO 64128, USA. sbanerjee2@kumc.edu
authors.forename: Snigdha
authors.initials: S
authors.lastname: Banerjee
authors.forename: Neela
authors.initials: N
authors.lastname: Saxena
authors.forename: Krishanu
authors.initials: K
authors.lastname: Sengupta
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Mayo
authors.forename: Sushanta K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055511:CCN Intercellular Signaling Proteins; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D004965:Estrogen Antagonists; D004967:Estrogens; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D014157:Transcription Factors; D003609:Dactinomycin; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol