2009 Nobel Prize in physiology and medicine awarded for an enzyme in cancer

Abstract

In 2009, the Nobel Prize in Physiology and Medicine was awarded to Drs Elizabeth H Blackburn (University of California, San Francisco, CA, USA), Carol W Greider (Johns Hopkins University School of Medicine, Baltimore, MD, USA) and Jack W Szostak (Harvard Medical School, Boston, MA, USA) who discovered telomerase. Their seminal work was the discovery of telomeres (i.e. the ends of chromosomes) from the ciliate Tetrahymena to be lengthened in yeast7 and that telomerase was responsible for the telomere lengthening activity by making telomere DNA.8 Investigations into telomerase, particularly its role in cancer, has advanced significantly since then. The ability of tumour cells to bypass senescence by circumventing telomere attrition and subsequently becoming immortal is considered a critical step in the progression of normal cells to cancerous cells. In this issue of the Journal, Liu et al. review recent new findings as to how telomerase is activated at the gene transcription level in breast cancer2 and how to control cancer by inhibiting the action of telomerase in the nucleus on the cell surface of cancer cells. Several lines of evidence support the concept that activation of telomerase in cancer is critically controlled at the level of gene transcription of telomerase reverse transcriptase (TERT) by the transcription factor Ets2.2 Therefore, the finding that silencing Ets2 suppresses telomerase activity and triggers breast cancer cell death has led to an assumption that Ets2 is a molecular target for the inhibition of telomerase in cancer.2 Dwyer and Liu2 have also suggested that the involvement of Ets2 in telomerase activation in cancer is apparently specific to breast cancer (cf. cervical cancer). In addition, it has been suggested that both breast and cervical cancer cells can be controlled using the cytokine bone morphogenetic protein (BMP)-7 to trigger telomerase repression and telomere attrition.3 This strategy of targeting telomerase and telomeres by using inhibitory cytokines has proven to be effective in immune-deficient mice with xenografted tumours receiving injections of BMP-7.