National Cancer Research Institute South of England
Prostate Cancer Collaborative
Research

Preliminary investigation of a possible mechanism of the tumourigenicity-suppressing activity of TIG1 in prostate cancer cells

Author

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:

  1. Ke YQ, et al., Anal. Biochem . 1999 , 269: 201-204.
  2. Ke YQ, et al., Nucleic Acids Res .   1999, 27: 912-914.
  3. Jing C, et al., Anal. Biochem. 2000, 287: 334-337.
  4. Jing C, et al., Cancer Res. 2000, 60: 2390-2398.
  5. Jing C, et al., Cancer Res. 2001, 61: 4357-4364.
  6. Adamson J, et al., Oncogene 2003, 22: 2739-2749.
  7. Nagpal S, et al., J. Invest. Dermatol. 1996, 106: 269-274.
  8. Jing C, et al., J. Natl. Cancer Inst. 2002, 94: 482-490.

 

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