News Release

Other highlights in the April 3 issue of JNCI

Peer-Reviewed Publication

Journal of the National Cancer Institute

TIG1 Identified as Tumor Suppressor Gene for Prostate Cancer
A new study has identified tazarotene-induced gene 1 (TIG1) as a possible tumor suppressor gene for prostate cancer, and experimental results suggest that decreased expression of the gene may play a role in the progression of prostate cancer.

Chun Jing, Youqiang Ke, Ph.D., and colleagues at the University of Liverpool, United Kingdom, compared genes expressed in malignant prostate cancer cells with those expressed in normal cells of the same tissue to identify oncogenes and tumor suppressor genes. TIG1, a retinoic acid receptor-responsive gene, was expressed in normal prostate tissue and in all 51 benign prostatic hyperplastic tissue samples but in only four of 51 malignant prostate tissue samples.

After inserting TIG1 into a highly malignant prostate cancer cell line, the authors showed that both the invasiveness and the ability of the cells to produce tumors were reduced. The authors conclude that TIG1 may be a tumor suppressor gene whose diminished expression may be involved in the malignant progression of prostate cancer. Their results appear in the April 3 issue of the Journal of the National Cancer Institute.

Marker for Progression of Colon Cancer Identified
Researchers have used gene expression profiles to identify a marker of colon cancer progression through a method called sample pooling. The results appear in the April 3 issue of the Journal of the National Cancer Institute.

Common changes in a gene expression profile can signal tumor progression. However, detecting such changes through gene expression profiling alone is an extremely complex task.

Deepak Agrawal, Timothy J. Yeatman, M.D., of the H. Lee Moffitt Cancer Center, Tampa, and colleagues investigated the feasibility of sample pooling in combination with a novel analysis algorithm to identify markers. RNA from 60 human colon tumors of multiple stages were pooled according to the stage of disease and compared with 10 normal mucosal specimens. More than 300 candidate tumor markers were identified, 11 of which were validated with further experiments.

The authors found that the gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in relation to the stage of the tumor. They conclude that the sample pooling approach can effectively identify the most common changes in a gene expression profile and that osteopontin is a useful marker of tumor progression in colon cancer.

Also in the April 3 JNCI:

  • Effects of depsipeptide in lung cancer cell lines: The histone deacetylase inhibitor depsipeptide FR901228 (FK228) is a novel antitumor agent in early clinical development for its toxic effects on tumor cells. However, the mechanism for this effect is unknown. Xiaodan Yu, David S. Schrump. M.D., and colleagues from the National Cancer Institute found that, in addition to promoting histone acetylation, FK228 modulates the expression of a variety of cell-cycle-related proteins, stabilizes wild-type p53 protein levels, and depletes mutant p53.

  • Cancer-specific expression of the survivin promoter: Survivin, an inhibitor of apoptosis, appears to be overexpressed in common cancers but is not expressed in corresponding normal adult tissues. Rudi Bao, Thomas C. Hamilton, Ph.D., and colleagues at the Fox Chase Cancer Center, Philadelphia, investigated whether the promoter for the survivin gene controls cancer-specific gene expression. They found that survivin expression appears to be, at least in part, transcriptionally activated in cancer cells specifically. They conclude that the survivin promoter may be useful in applications such as driving transgene expression in a cancer cell-specific manner for gene therapy.

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