Embryonic retinal tumors in SV40 T-Ag transgenic mice contain CD133+ tumor-initiating cells.

Investigative Ophthalmology & Visual Science
Lalita WadhwaRichard L Hurwitz

Abstract

Human retinoblastomas form during the proliferative phase of retina development and are caused by mutations that result in absent or functionally defective Rb protein. Similar tumors occur in mice only when multiple Rb gene family members are absent. We asked if retinal tumors can arise from an undifferentiated retinal cell. The tumor-initiating cells isolated from these tumors that formed in early embryonic murine retinas were characterized. Transgenic mice were created using a Pax6 promoter to target expression of SV40 large T-antigen (T-Ag) in the undifferentiated murine embryonic retina. T-Ag, which sequesters all Rb family proteins and p53, is expressed in the retina and lens by murine embryonic day 10 (E10) and tumors are observed by E12.5. A cell line that is adherent in serum-containing media and forms neurospheres in supplemented serum-free media was developed from retinal tumors isolated on postnatal day 7. In all, 1.5% of attached cells form neurospheres when transferred to serum-free medium. All cultured cells express T-Ag, confirming that they derive from the original tumors; 0.5% of adherent cells express detectable levels of CD133. CD133+ FACS-sorted cells cultured in serum-free medium form 3-fold more neurospher...Continue Reading

Citations

Dec 1, 2015·Archives of Pathology & Laboratory Medicine·Jesús R GarciaPatricia Chévez-Barrios
Mar 4, 2014·Seminars in Cell & Developmental Biology·Emily K ColvinAmanda L Hudson
Nov 15, 2013·Saudi Journal of Ophthalmology : Official Journal of the Saudi Ophthalmological Society·Rohini M NairGeeta K Vemuganti

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