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Titolo:
Wnt-1 and int-2 mammary oncogene effects on the beta-catenin pathway in immortalized mouse mammary epithelial cells are not sufficient for tumorigenesis
Autore:
Hollmann, CA; Kittrell, FS; Medina, D; Butel, JS;
Indirizzi:
Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 l & Microbiol, Houston, TX 77030 USA Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 Cellular Biol, Houston, TX 77030 USA
Titolo Testata:
ONCOGENE
fascicolo: 52, volume: 20, anno: 2001,
pagine: 7645 - 7657
SICI:
0950-9232(20011115)20:52<7645:WAIMOE>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST GROWTH-FACTOR; HUMAN BREAST-CANCER; GENE-PRODUCT ACTS; TRANSGENIC MICE; E-CADHERIN; PROVIRAL ACTIVATION; TUMOR DEVELOPMENT; COLON-CARCINOMA; CELLULAR GENE; LINES INVITRO;
Keywords:
mammary oncogenes; wnt-1; int-2; mammary epithelial cells; mammary tumorigenesis; mouse model for breast cancer; signal transduction pathways;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Butel, JS Baylor Coll Med, Dept Mol Virol & Microbiol, Mail Stop BCM 385,1Baylor Plaza, Houston, TX 77030 USA Baylor Coll Med Mail Stop BCM 385,1 Baylor Plaza Houston TX USA 77030
Citazione:
C.A. Hollmann et al., "Wnt-1 and int-2 mammary oncogene effects on the beta-catenin pathway in immortalized mouse mammary epithelial cells are not sufficient for tumorigenesis", ONCOGENE, 20(52), 2001, pp. 7645-7657

Abstract

Development of strategies for prevention of breast cancer development requires an understanding of the effects of mammary oncogenes on mammary cells at early stages in neoplastic transformation. As mammary oncogenes wnt-1 and int-2 affect different signal transduction pathways, we investigated their effects on established mouse mammary epithelial cell lines (MMECLs) reflecting early stages in tumorigenesis. Normal interactions between beta -catenin and E-cadherin were abrogated in all three immortalized MMECLs and the cells lacked beta -catenin-mediated transactivation activity, detectable using a reporter assay, suggesting that alterations in cell adhesion may be very early events in mammary tumorigenesis. Immortalized FSK4 and EL12 cellsand hyperplastic TM3 cells were stably transfected with expression vectorsencoding wnt-1 or int-2 or the control vector, and drug-selected pooled cells from each tine were confirmed by reverse transcription-polymerase chainreaction to express the transfected oncogene; this expression persisted inthe cells analysed in vitro and in vivo. Resultant phenotypic changes depended both on the oncogene and the target mammary cell line. In FSK4 cells, expression of wnt-1 or int-2 resulted in proliferative changes in vitro, including reduced contact inhibition, increased beta -catenin expression, anddecreased p53 transcriptional activity, but neither oncogene conferred upon those cells the ability to produce tumors in vivo. EL12 cells were highlyrefractory to the effects of both oncogenes, with the only measurable changes being increased E-cadherin levels induced by both oncogenes and increased proliferation of the int-2-transfected cells in the absence of serum. Parental TM3 cells were phenotypically similar to wnt-1- or int-2-transfectedFSK4 cells and displayed an increased rate of proliferation in vitro and markedly increased tumorigenicity in vivo following transfection with int-2 but not with wnt-1. These results suggest that wnt-1 signaling is redundantin the hyperplastic TM3 cells and indicate that wnt-1-induced effects in the immortalized FSK4 and EL12 cells were not sufficient to mediate a tumorigenic phenotype. This study showed that the wnt-1 and int-2 oncogenes have similar but distinguishable effects on immortalized MMECLs and that the genetic background of the mammary cells greatly influences the consequences ofoncogene expression at early stages of cell transformation.

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Documento generato il 06/04/20 alle ore 01:42:51