Tumour suppressors

DBC2 , a candidate for a tumor suppressor gene involved in breast cancer.

Hamaguchi, M. et al. Proc. Natl Acad. Sci. USA 99, 13647?13652 (2002)

Tumour suppressors such as BRCA1 and BRCA2, which are mutated in familial breast cancer, have previously been identified, but what of those that are responsible for sporadic breast cancer? The gene deleted in breast cancer (DBC2) was cloned from chromosome 8p21, following the discovery that this region is deleted in some breast cancers. It is homozygously deleted in 3.5% of breast tumours analysed. Expression of wild-type, but not mutated, DBC2 in breast cancer cells inhibits their growth.

Prostate cancer

The polycomb group protein EZH2 is involved in progression of prostate cancer.

Varambally, S. et al. Nature 419, 624?629 (2002)

Metastatic prostate cancer is essentially incurable, so the identification of genes that are involved in its progression to this stage is an important task. Gene-expression profiling has revealed that the polycomb protein EZH2 ? a transcriptional repressor ? is overexpressed in hormone-refractory metastatic prostate cancer. Its overexpression in localized prostate cancer also indicates a poorer prognosis, so it might be involved in progression of prostate cancer, as well as being a marker of metastatic cancer.

Angiogenesis

PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis.

Panigrahy, D. et al. J. Clin. Invest. 110 923?932 (2002)

The PPARγ nuclear receptor is known to inhibit growth and/or induce differentiation in cancer cells, and Dipak Panigrahy et al. now report that it is highly expressed by the endothelial cells that surround the tumour. The PPARγ ligand rosiglitazone was shown to suppress both primary tumour growth and metastasis by inhibiting angiogenesis ? it decreases production of VEGF. By inhibiting angiogenesis, PPARγ ligands could therefore be a useful anticancer therapeutic strategy.

Apoptosis

BID regulation by p53 contributes to chemosensitivity.

Sax, J. K. et al. Nature Cell Biol. 4, 842?849 (2002)

Chemotherapy acts against cancer cells by damaging their DNA to such an extent that the cells undergo apoptosis. This response is mediated by the transcriptional regulator and tumour suppressor p53, but the target genes that are involved have not been fully elucidated. Wafik El-Deiry and colleagues show that the pro-apoptotic gene BID ? a member of the BCL2 family ? is upregulated in response to γ-irradiation, and that mice deficient for Bid are resistant to the chemotherapeutic adriamycin. BID is therefore a p53-responsive chemosensitivity gene.