Characterization of WWOX Inactivation in Murine Mammary Gland Development
| dc.contributor.author | Abdeen, Suhaib K. | |
| dc.contributor.author | Salah, Zaidoun | |
| dc.contributor.author | Khawaled, Saleh | |
| dc.contributor.author | Aqeilan, Rami I. | |
| dc.date.accessioned | 2018-09-29T13:32:17Z | |
| dc.date.available | 2018-09-29T13:32:17Z | |
| dc.date.issued | 2012-12-18 | |
| dc.description.abstract | The WW domain-containing oxidoreductase (WWOX) is commonly inactivated in multiple human cancers, including breast cancer. Wwox null mice die prematurely precluding adult tumor analysis. Nevertheless, aging Wwox-heterozygous mice at C3H genetic background develop higher incidence of mammary tumors. We recently generated a Wwox conditional knockout mouse in which loxp sites flank exon 1 in the Wwox allele and showed that total ablation of WWOX in these mice resembles that of conventional targeting of Wwox. Here, we report the characterization of WWOX ablation in mouse mammary gland using MMTV-Cre transgenic line. We demonstrated that WWOX ablation leads to impaired mammary ductal growth. Moreover, targeted deletion of WWOX is associated with increased levels of fibronectin, a component of the extracellular matrix. In addition, we showed that shRNA knockdown of WWOX in MCF10A breast epithelial cells dramatically increased fibronectin and is associated with enhanced cell survival and impaired growth in three-dimensional culture Matrigel assay. Taken together our results are consistent with a critical role for WWOX in normal breast development and tumorigenesis. | en_US |
| dc.description.sponsorship | Authors are grateful to Norma Qidees for technical help in histology and for Sara Del-Mare, Mohammad Abu-Odeh, and Ella Abaktekov for technical assistance. This work was supported by the Israeli Science Foundation grant (ISF #08- 1331), EU-FP7 Marie Curie Re-integration grant to R.I.A. and Israeli Cancer Research Funds (ICRF) to Z.S. and NIH R01 DK079217 from NIDDK. | en_US |
| dc.identifier.issn | 1097-4652 | |
| dc.identifier.uri | https://dspace.alquds.edu/handle/20.500.12213/1020 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Wiley Periodicals, Inc. | en_US |
| dc.title | Characterization of WWOX Inactivation in Murine Mammary Gland Development | en_US |
| dc.type | Article | en_US |