Retinoblastomas appear to be derived from a multipotential stem cell of the retina, due to alterations of the Rb I gene. These tumors arise only within a discrete time frame during childhood, prior to terminal differentiation of the retinal precursor cells. Treatment of retinoblastoma cells with certain agents can induce a partial differentiation of cell types resembling those of the mature retina, such as rod and cone photoreceptors, glia, conventional neurons and pigment epititelia. We have tested the effects of 8-CI-cAMP, a synthetic analog of cAMP which preferentially binds to and activates the RII subunit of protein kinase A on the Y-79 retinoblastoma cell line in vitro. Y-79 cells treated with 8-CI-cAMP produced short, branching processes and showed a substantial increase in staining for neuron-specific enolase, a marker for conventional neuronal differentiation. In contrast, dibutyryl-cAMP gives a strong increase in the glial marker glial acidic fibrillary protein. Y-79 cell proliferation was strongly inhibited by 8-CI-cAMP at concentrations as low as 5-25 mu M. 8-CI-cAMP significantly increased the rate of apoptosis of Y-79 cells in a dose-dependent manner. It also modulated expression of the RI regulatory subunit of intracellular cAMP-dependent protein kinase A, which is produced in abnormal quantities by Y-79 cells. A decrease in protein production was observed, with no clear effect on the RI subunit mRNA expression, suggesting that RI regulation occurs posttranscriptionally
The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells / Gianfranco Fassina;M.G. Aluigi;Susan Gentleman;Paul Wong;Tania Cai;Adriana Albini;Douglas M. Noonan. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - STAMPA. - 72(1997), pp. 1088-1094.
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Titolo: | The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells |
Autori: | |
Data di pubblicazione: | 1997 |
Rivista: | |
Citazione: | The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells / Gianfranco Fassina;M.G. Aluigi;Susan Gentleman;Paul Wong;Tania Cai;Adriana Albini;Douglas M. Noonan. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - STAMPA. - 72(1997), pp. 1088-1094. |
Abstract: | Retinoblastomas appear to be derived from a multipotential stem cell of the retina, due to alterations of the Rb I gene. These tumors arise only within a discrete time frame during childhood, prior to terminal differentiation of the retinal precursor cells. Treatment of retinoblastoma cells with certain agents can induce a partial differentiation of cell types resembling those of the mature retina, such as rod and cone photoreceptors, glia, conventional neurons and pigment epititelia. We have tested the effects of 8-CI-cAMP, a synthetic analog of cAMP which preferentially binds to and activates the RII subunit of protein kinase A on the Y-79 retinoblastoma cell line in vitro. Y-79 cells treated with 8-CI-cAMP produced short, branching processes and showed a substantial increase in staining for neuron-specific enolase, a marker for conventional neuronal differentiation. In contrast, dibutyryl-cAMP gives a strong increase in the glial marker glial acidic fibrillary protein. Y-79 cell proliferation was strongly inhibited by 8-CI-cAMP at concentrations as low as 5-25 mu M. 8-CI-cAMP significantly increased the rate of apoptosis of Y-79 cells in a dose-dependent manner. It also modulated expression of the RI regulatory subunit of intracellular cAMP-dependent protein kinase A, which is produced in abnormal quantities by Y-79 cells. A decrease in protein production was observed, with no clear effect on the RI subunit mRNA expression, suggesting that RI regulation occurs posttranscriptionally |
Handle: | http://hdl.handle.net/11567/388589 |
Appare nelle tipologie: | 01.01 - Articolo su rivista |