Cyclin D1 and p21 is elevated in the giant cells of
giant cell tumors.
Kandel
R, Li SQ, Bell R, Wunder
J, Ferguson P,
Kauzman
A, Diehl JA, Werier
J.
Department of Laboratory Medicine and Pathobiology,
Mount Sinai Hospital, 600
University Avenue, Suite 600, Toronto, Ontario M5X 1G5 Canada.
Alterations of cell cycle regulatory proteins, especially those that
regulate G1 to S transition, have been implicated in the pathogenesis of a
wide variety of human tumors. In previous studies we showed that that there
is overexpression of cyclin
D1 protein predominately in the giant cell component of giant cell tumors
of bone. The purpose of this study was to investigate the mechanisms that may
be responsible for cyclin D1 accumulation in
giant cell tumors. Giant cell tumors have high levels of cyclin D1 mRNA and the giant cell-enriched population of these tumors have significantly more mRNA
and protein expression of cyclin D1 than the
mononuclear cell population. The giant cells also expressed higher levels
of p21 protein and more p21 bound to cyclin D1
than the mononuclear cells. It is possible that p21 may be contributing to
the cyclin D1 accumulation that occurs in the
giant cells and perhaps even giant cell formation in these tumors.
Additional studies are required to confirm the role of p21 in the
pathogenesis of these tumors. (c) 2006 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:428-437, 2006.
PMID: 16479604 [PubMed - as supplied by
publisher]
Direct Interaction of p21 with p50, the Small
Subunit of Human DNA Polymerase Delta.
Li H, Xie
B, Rahmeh
A, Zhou Y, Lee MY.
Department of Biochemistry and Molecular Biology, New York Medical College,
Valhalla, New York, USA.
Using a yeast two-hybrid screening technique and the p50 subunit of human
DNA polymerase delta (pol delta) as a bait, p21 was found to interact with the p50 subunit
of pol delta. A direct interaction between p21
and p50 was confirmed by using ELISA and pull-down assays with purified
proteins. The interaction sites between p50 and p21 were mapped by pull
down assays with GST deletion mutants. Residues 127-193 constitute the
primary interaction region on p50 to which p21 binds, while p50 binds to
the C-terminal 26 residues of p21. A histone kinase activity was associated with the highly purified
calf thymus pol delta and addition of purified
recombinant p21 inhibited the kinase activity in
a dose dependent manner. p50 is phosphorylated in vivo and can be phosphorylated
by CDK2/cyclinA in vitro. In vivo evidence of p21 association with p50 was
obtained by coimmunoprecipitation using MCF7
cells. It was also shown that the association of p21 with p50 and other
components of the pol delta complex increased in
MCF7 cells treated with adriamycin.
Our results suggested that p50 might target or anchor p21 to pol delta complex upon certain DNA damage such as adriamycin treatment.
PMID: 16479163 [PubMed - as supplied by publisher
Adenovirus-Mediated
p53 Treatment Enhances Photodynamic Antitumor
Response.
Lim DS, Bae
SM, Kwak
SY, Park EK, Kim JK, Han SJ, Oh CH, Lee CH, Lee WY, Ahn
WS.
Cancer Research Institute of Medical Science, The Catholic
University of Korea,
Seoul 137-040, South
Korea.
Photodynamic therapy (PDT) has been reported to be effective for treating
various tumors and to induce apoptosis in many tumor cells. In this study,
we evaluated the ability of PDT combined with a tumor suppressor factor,
recombinant adenovirus p53 (AdCMVp53), to induce apoptosis as well as cell
growth inhibition in CaSki human cervical cancer
cells and in nude mice with implanted CaSki
cells. To examine levels of apoptosis, CaSki
cells were treated with PDT and/or AdCMVp53, and an annexin
V-staining assay was then conducted. In addition, Western blot analysis was
done to identify p53 induction at the cellular and tumor tissue levels.
PDT+AdCMVp53 cotreatment caused remarkable
inhibition of CaSki cell proliferation, as
compared with the individual treatments. In parallel with the inhibition of
cell proliferation, the cotreatment caused a
significantly greater increase in the annexin
V-stained cell population compared with the individual treatments, as
determined by fluorescence-activated cell-sorting analysis. The Western blotting
assay also showed significantly more cellular p53 expressed after
PDT+AdCMVp53 cotreatment than after each separate
treatment. This was consistent with observations of tumor tissue in the
mouse system. However, apoptosis- related protein, p21, was significantly
suppressed by PDT+AdCMVp53 cotreatment, contrary
to treatment with AdCMVp53 alone. Taken together, these findings suggest
that PDT plus AdCMVp53 gene therapy exerts more potent antitumor
effects on human cervical cancer cells, with induction of apoptosis at
least through activation in p53 protein at the cellular and tumor tissue
levels.
PMID: 16478390 [PubMed - as supplied by
publisher]
