Retinoblastoma is the most common intraocular tumor in childhood and its origin is in the embryonal layer, the neuroectoderm. It shares some histopathological and biological features with other neoplasms of the central nervous system (neuroblastoma). Flexner-Wintersteiner rosettes and fleurettes in differentiated retinoblastoma was interpreted as photoreceptor cell differentiation, however, no molecular and biochemical markers have yet been described supporting this hypothesis. Our in vitro culture system allows for the routine growth and amplification of primary retinoblastoma cells. We documented by light and electron microscopy the differentiation of retinoblastoma into Flexner-Wintersteinder rosettes in vitro. It is the goal of this proposal to characterize retinoblastoma with cell and tissue specific markers (intermediate filaments), retina specific markers (rhodopsin and transducin) and embryonic regulatory markers (homeotic genes) using our established culture system. Expression of GFAP will demonstrate glial cell and astrocyte differentiation in retinoblastoma previously suggested. Analysis of expression of rhodopsin and/or transducin using cDNA probes will for the first time demonstrate photoreceptor cell specific markers in this tumor and therefore support the original hypothesis. Homeotic genes are regulatory genes whose activities are vital for normal pattern formation, embryonic development and cell differentiation. We hypothesize that these regulatory genes like the N-myc oncogene are involved in the penetration of the cancer phenotype in this embryonal tumor. We will compare the expression or homeotic genes and N-myc oncogene in differentiating retinoblastoma and the developing retina in order to establish correlations between oncogene and homeotic gene expression and their roles in the development of neural crest tumors.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY004950-04
Application #
3259621
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-07-01
Project End
1989-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
094878337
City
Los Angeles
State
CA
Country
United States
Zip Code
90027
Chen, J; Tucker, C L; Woodford, B et al. (1994) The human blue opsin promoter directs transgene expression in short-wave cones and bipolar cells in the mouse retina. Proc Natl Acad Sci U S A 91:2611-5
Matsushima, H; Bogenmann, E (1993) Expression of trkA cDNA in neuroblastomas mediates differentiation in vitro and in vivo. Mol Cell Biol 13:7447-56
Hiti, A L; Bogenmann, E; Gonzales, F et al. (1989) Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas. Mol Cell Biol 9:4722-30
Bogenmann, E; Lochrie, M A; Simon, M I (1988) Cone cell-specific genes expressed in retinoblastoma. Science 240:76-8
Friend, S H; Dryja, T P; Weinberg, R A (1988) Oncogenes and tumor-suppressing genes. N Engl J Med 318:618-22
Bogenmann, E; Moghadam, H; DeClerck, Y A et al. (1987) c-myc amplification and expression in newly established human osteosarcoma cell lines. Cancer Res 47:3808-14
Scott-Burden, T; Bogenmann, E; Jones, P A (1986) Effects of complex extracellular matrices on 5-azacytidine-induced myogenesis. Exp Cell Res 164:527-35
Bogenmann, E (1986) Retinoblastoma cell differentiation in culture. Int J Cancer 38:883-7