Downregulation of Wilms' tumor 1 protein inhibits breast cancer proliferation.
High levels of Wilms' Tumor 1 (WT1) mRNA have been correlated with poor prognosis in breast cancer patients. However, the function of WT1 protein in breast cancer is not known. We observed that the levels of WT1 protein correlated with the proliferation of breast cancer cells. When the proliferation of breast cancer cells was stimulated by 17beta-estradiol, WT1 protein expression increased. But when the proliferation of breast cancer cells was inhibited by tamoxifen or all-trans retinoic acid (ATRA), WT1 protein expression decreased. We hypothesize that WT1 protein plays a role in regulating breast cancer cell proliferation. Using liposome-incorporated WT1 antisense oligodeoxynucleotides, we found that downregulation of WT1 protein expression led to breast cancer growth inhibition and reduced cyclin D1 protein levels. These results indicate that WT1 protein contributes to breast cancer progression by promoting breast cancer cell proliferation.
Department of Bioimmunotherapy, Section of Immunobiology and Drug Carriers, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 422, Houston, TX 77030, USA.
Pablo
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Zapata-Benavides
Musaffe
M
Tuna
Gabriel
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Lopez-Berestein
Ana M
AM
Tari
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000096:biosynthesis*
D018931:Antineoplastic Agents, Hormonal; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D025721:WT1 Proteins; D013629:Tamoxifen; D004958:Estradiol