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The dynamics of hormone-induced gene movement in normal and cancer cells

Michal Schwartz

Appointment Period: 2008-2009 / Grant Year: [24]

Michal SchwartzThe aim of my work is to study the potential contribution of non-random gene positioning in the cell’s nucleus, induced by hormonal stimulation, to the occurrence of genomic rearrangements in prostate and breast cancer.

One of the hallmarks of cancer is rearrangement of the genetic material. These rearrangements can lead to dramatic changes in the activity of genes that promote the progression of cancer. One type of rearrangement, known as chromosome translocation, involves the joining of two parts of chromosomes that are naturally not joined together. These translocations tend to occur at the same genomic locations in different cancer patients, and the reason for that is not well understood. In the past few years, based on the realization that the spatial organization of the genome in the nucleus is non-random, it has been suggested that the proximity between two gene loci generated by this non-random spatial organization contributes to recurrent tumor translocations.

The aim of my research is to analyze the dynamics of movement of nuclear receptor target genes in the 3D nuclear space as a potential contributor to the occurrence of translocations in cancer. For that I have established a cell-based system that allows tracking of the position of specific genes in the nucleus in live cells. This system allows to fluorescently track movement of specific genes in live cells in response to different stimuli, such as hormone stimulation, which may play a role in the progression of different forms of cancer, such as prostate and breast cancer. This system will be used to analyze differences between normal and cancer cells in the dynamics of movement of nuclear receptor target genes in response to hormone stimuli that may contribute to the occurrence of translocations in cancer cells by creating spatial proximity between different genes.

This work will shed light on the molecular mechanism leading to recurrent translocations in breast and prostate cancer, induced by the activity of estrogen and androgens, respectively.

Ozeri-Galai E, Schwartz M, Rahat A, Kerem B. Interplay between ATM and ATR in the regulation of common fragile site stability. Oncogene. (2008) 27(15):2109-17. PMID: 17934520.