Notch1-Induced Transformation of RKE-1 Cells Requires Up-regulation of Cyclin D1

Stahl, Mark; Ge, Changrong; Shi, Shaolin; Pestell, Richard G.; Stanley, Pamela

doi:10.1158/0008-5472.can-06-0974

Cited by 50 publications

(39 citation statements)

References 54 publications

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“…Their early expansion correlates closely with later tumor formation, and abrogation of this early expansion in cyclin D1-deficient mice also correlates with the absence of tumors in these KO mice. This latter result extends a previous report showing that in vitro transformation of RKE-1 cells by N1 IC requires cyclin D1 (Stahl et al, 2006).…”

Section: Discussionsupporting

confidence: 91%

Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors

2010

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Members of the Notch family are involved in the development of breast cancer in animal models and in humans. In young transgenic mice, expressing intracellular activated Notch1 (N1 IC ) in mammary cells, we found that CD24 þ CD29 high progenitor cells had enhanced survival, and were expanded through a cyclin D1-dependent pathway. This expansion positively correlated with the later cyclin D1-dependent formation of basal-like ductal tumors. This expanded population exhibited abnormal differentiation skewed toward the basal cells, showed signs of pre-malignancy (low PTEN/p53 and high c-myc) and contained stem cells with impaired selfrenewal in vivo, and more numerous multipotent, ductalrestricted progenitors. Our data suggest that N1 IC can favor transformation of progenitor cells early in life through a cyclin D1-dependent pathway.

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Section: Discussionsupporting

confidence: 91%

Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors

2010

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“…Our in vitro findings showed that Notch expression was associated with TEC proliferation and cyclin D1 expression (as also described in other cells; ref. 37). Coculturing Jag1expressing stromal cells with TECs or fibroblasts was also sufficient to induce expression of cyclin D1, both in epithelial cells and in fibroblasts (data not shown).…”

Section: Discussionmentioning

confidence: 86%

Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans

et al. 2010

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“…Cyclin D1 expression during development was shown to correlate with the expression of Notch, and cyclin D1 was required for Notch1-mediated transformation and contact-independent growth. 89 Subsequent studies in breast cancer cells demonstrated that cyclin D1 enhances Notch1 activity by inhibiting the expression of its negative regulator, Numb. 90 Consistent with these findings, cyclin D1 knockout mice showed resistance to Notch1-induced mammary tumorigenesis.…”

Section: Micrornasmentioning

confidence: 99%

The Role of Breast Cancer Stem Cells in Metastasis and Therapeutic Implications

Velasco-Velázquez

Попов

Lisanti

et al. 2011

The American Journal of Pathology

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155

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Cancer stem cells (CSCs) are tumor cells that possess the capacity to divide asymmetrically, producing one stem cell (self-renewal) and one progenitor cell that is able to generate heterogeneous lineages of the cancer cells that comprise tumors. CSCs in human breast tumors were initially identified in 2003 by Al-Hajj et al, 1 who discovered a cellular population characterized by the cell-surface markers CD44 ϩ /CD24 Ϫ/low /ESA ϩ and lack of expression of CD2, CD3, CD10, CD16, CD18, CD31, CD64, and CD140b (lineage Ϫ ). As few as 200 of these cells were able to form tumors when xenotransplanted into NOD/SCID mice, whereas tens of thousands of other cells could not.1 The tumors generated recapitulated the phenotypic heterogeneity of the parental tumor, containing a minority of CD44 ϩ /CD24 Ϫ/low /lineage Ϫ cells that can be serially passaged to form new tumors.1 The CD44 ϩ /CD24 Ϫ phenotype has been used extensively to identify and isolate breast cancer cells with increased tumorigenicity.Putative breast CSCs have also been isolated from patient samples after in vitro propagation and from breast cancer cell lines, through their ability to proliferate in suspension as nonadherent spheres (mammospheres). 1-4Because the capacity to form mammospheres is increased in early progenitor/stem cells, this system has been widely used as an indirect measurement of the number of cells with self-renewal capability. 5,6 In accord with in vivo data, mammospheres from breast cancer cells are enriched in cells with the CD44 ϩ /CD24 /CD24Ϫ retain self-renewal capability, other markers for human breast CSCs have been investigated. Activity of the aldehyde dehydrogenase (ALDH) family of cytosolic isoenzymes is inSupported in part by PASPA-UNAM (Programa de Apoyos para la Superación del Personal Académico-Universidad Nacional Autónoma de México) (M.A.V.-V.) and the NIH (grants R01CA070896, R01CA075503, R01CA107382, R01CA132115, and R01CA086072 to R.G.P. and R01CA120876 to M.P.L.). The Kimmel Cancer Center was supported by an NIH cancer center core grant (P30CA56036 to R.G.P.). This project is funded in part from the Marian C. Falk Medical Research Trust and a grant from the Pennsylvania Department of Health (R.G.P.).

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Notch1-Induced Transformation of RKE-1 Cells Requires Up-regulation of Cyclin D1

Abstract: RKE-1 cells induced to overexpress activated Notch1 (RKE-ER-N ic

Cited by 50 publications

References 54 publications

Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors

Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors

Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans

The Role of Breast Cancer Stem Cells in Metastasis and Therapeutic Implications

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