2002
CTOS Annual Meeting Posters
— Pathology
DIFFERENTIAL
EXPRESSION OF CELL CYCLE G1 CYCLINS IN EWING TUMORS AND RHABDOMYOSARCOMA
[Abstract
ID: 54]
Category:
Pathology
Authors:
Jingsong Zhang1, Deborah E. Schofield1, Timothy
J. Triche1
Author Institutions:
1Childrens Hospital Los Angeles Research Institute, California,
United States
Presenter:
Jingsong Zhang
jzhang@chla.usc.edu
Correspondent: Jingsong Zhang
jzhang@chla.usc.edu
Los Angeles California United States CA 90027
Ph: 323-669-5609
Fax: 323-906-8081
Objectives: Ewing
tumors (ET) and rhabdomyosarcoma (RMS) are two common musculoskeletal
tumors of childhood and adolescence. To understand the oncogenic
pathways underlying their uncontrolled proliferation, we focused
on the expression and function of cell cycle G1 regulators in these
two tumors.
Methods: The expression profile of cell cycle regulators
in 7 ET and 13 RMS primary tumor samples generated by the Affymetrix's
U95Av2 array was first studied and the observed gene expression
patern was then validated in 7 ET cell lines and 6 RMS cell lines
with quantitive RT-PCR and western blot.
Results: Primary tumors of ET and RMS could be distinguished
by hierarchical clustering of 10 probe sets for the 5 G1 cyclins.
Consistent with previous findings, the three probe sets for CCND1
were consistently high in all 7 ET samples and consistently low
in all 13 RMS samples. Unlike ET, RMS samples had high levels of
cyclin D2, cyclin D3, and cyclin E1 expression. Expression level
of cyclin E2 varies among ET and RMS samples. The same expression
pattern of G1 cyclins was detected in ET and RMS cell lines at both
RNA and protein levels. Furthermore, the dominantly expressed G1
cyclins play a major role in regulating the RB pathway of cell cycle
G1 control as reflected by their association with the cyclin dependent
kinases and phosphorylation of pRb.
Conclusions: ET and RMS over-express different G1 cyclins
to acelerate cell cycle progression. Identification of the underlying
pathways may highlight strategic targets for developing tumor specific
treatment.
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