Preliminary investigation
of a possible mechanism of the tumourigenicity-suppressing activity
of TIG1 in prostate cancer cells
Author
Dr Y
Ke
University
of Liverpool
During the past a number
of years, our effort has been focused on the identification of genes
involved in the malignant progression of human prostate cancer.
Using several unique molecular biology approaches for systematic
analysing differential gene expression [1-3], we have successfully
identified a large number of candidate genes that expressed differentially
between the benign and the malignant prostate model cells. From
these candidate genes, we have successfully characterised several
genes [4-6] whose altered expression may have determined effect
on the development and metastasis of prostate cancer. F50 is
one of such characterised genes, which were previously related to
any malignant diseases. Nucleotide sequence analysis confirmed that
F50 is identical to the Tazarotene-Induced Gene 1 (TIG1),
a retinoic acid receptor-responsive gene that was originally isolated
from the skin [7]. Further investigation showed that although TIG1
is expressed abundantly in benign prostate cell lines and tissues,
its expression is diminished in malignant cell lines and prostate
carcinoma tissues. Transfection of TIG1 into a highly malignant
prostate cancer cell line PC-3M has greatly inhibited its in
vitro invasiveness and significantly reduced its tumourigenicity
when inoculated into nude mice. This date suggests that TIG1 may
be an important tumour suppressor gene and its diminished expression
may be involved in the malignant progression of prostate cancer
[8].
Although the identification
of the involvement of TIG1 in suppression of prostate cancer may
be potentially important, TIG1 cannot be used as a new target for
treatment before we have gained sufficient understanding on how
it works inside prostate cells. With the support of the Prostate
Collaborative Development Grant, we will conduct some explorative
investigations to study the possible molecular mechanisms involved
in the tumourigenicity-suppressing activity of the TIG1. We will
test a working hypothesis on how TIG1 can suppress tumourigenicity
of prostate cancer. We believe that through this explorative work,
we will be able collect sufficient preliminary data to enable us
to write an application for a three-year project grant to study
further the molecular mechanisms involved in the tumourigenicity-suppressing
activity of TIG1.
References:
- Ke YQ, et al., Anal. Biochem . 1999 , 269:
201-204.
- Ke YQ, et al., Nucleic Acids Res .
1999, 27: 912-914.
- Jing C, et al., Anal. Biochem. 2000, 287:
334-337.
- Jing C, et al., Cancer Res. 2000, 60:
2390-2398.
- Jing C, et al., Cancer Res. 2001, 61: 4357-4364.
- Adamson J, et al., Oncogene 2003, 22:
2739-2749.
- Nagpal S, et al., J. Invest. Dermatol. 1996, 106:
269-274.
- Jing C, et al., J. Natl. Cancer Inst. 2002, 94:
482-490.
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