THESIS
2012
xiii, 101 p. : ill. ; 30 cm
Abstract
RGS (regulator of G protein signaling) proteins serve as negative regulators of G protein
signaling. Since the discovery of the first RGS protein, more than 37 RGS members encoded
by the human genome have been identified. According to their RGS domain homology and
common functional domain architecture, RGS members are divided into eight subfamilies and
recent studies indicate that they may play multi-tasking roles in cellular regulation.
Although RGS20 is highly expressed in metastatic melanomas than in primary melanomas,
the role of RGS20 on tumorigenesis and metastasis remains unclear. To explore these
functions of RGS20, a constitutively active mutant of H-Ras (H-RasGV) was stably expressed
with or without RGS20 in NIH3T3 cells. Conversely, RGS20 was stably knocked down in
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RGS (regulator of G protein signaling) proteins serve as negative regulators of G protein
signaling. Since the discovery of the first RGS protein, more than 37 RGS members encoded
by the human genome have been identified. According to their RGS domain homology and
common functional domain architecture, RGS members are divided into eight subfamilies and
recent studies indicate that they may play multi-tasking roles in cellular regulation.
Although RGS20 is highly expressed in metastatic melanomas than in primary melanomas,
the role of RGS20 on tumorigenesis and metastasis remains unclear. To explore these
functions of RGS20, a constitutively active mutant of H-Ras (H-RasGV) was stably expressed
with or without RGS20 in NIH3T3 cells. Conversely, RGS20 was stably knocked down in
A549 human small lung cancer cell. Using these cellular models, it was shown that NIH3T3
fibroblasts lost contact inhibition upon expressing oncogenic Ras in adherent cultures. RGS20
enhanced cell aggregation in NIH3T3 fibroblasts expressing oncogenic Ras. Compared with
RGS20, RGS19 (which also belongs to the RZ subfamily) showed no significant effect on cell
aggregation in NIH3T3 fibroblasts. Cells lacking contact inhibition would consequently grow
into spheres which might reflect initial outgrowth of tumors. Additionally, in vitro
experiments showed that the knockdown of RGS20 reduced the migration and invasion ability
of A549 cells without influencing their proliferation rate.
These observations supported the hypothesis that RGS20 might have a role in potentiating
tumor metastasis by enhancing cell aggregation and migration. Further investigation of the
mechanisms or signaling pathways involved in these effects are required. These findings
support the notion that RGS proteins might serve additional functions other than being
GTPase accelerating proteins.
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