Requirement of Pygopus 2 in breast cancer.
The development of novel therapeutic strategies for breast cancer requires the identification of molecular targets involved in malignancy. Human Pygopus (Pygo)-1 and -2 are recently discovered components of the Wnt signaling pathway required for beta-Catenin/Tcf dependent transcription in embryos and colorectal cancer cells, but the role of these proteins in malignant cell growth and survival has not yet been determined. We report the expression and requirement for proliferation of hPygo2 in breast cancer cells. hPygo2 protein was overexpressed in malignant breast tumors and in the nuclei of five breast cancer cell lines, but was not expressed in the nuclei of non-malignant breast cells. Phosphorothioated antisense oligonucleotides were used to specifically knockdown expression hPygo2 in Mcf-7 and MDA-MB-468 cell lines. hPygo2 was required for the growth, in tissue culture and anchorage-independent assays, of both cell lines and for the expression of the Wnt target gene Cyclin D1. We conclude that hPygo2 is highly expressed in, and required for the growth of breast carcinoma cells.
Andrews
Phillip G P
PG
Terry Fox Cancer Research Laboratories, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, A1B 3V6, Canada.
Lake
Blue B
BB
Popadiuk
Catherine
C
Kao
Kenneth R
KR
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; C453401:PYGO2 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; D012313:RNA