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Breast cancer : Discovery of a new tumor marker

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02.04.2004

CAF-1 expression in cell nuclei
You can notice that the CAF-1 complex (in yellow) is present in the vast majority of proliferating cells (left panel). By contrast, it is hardly expressed in resting cells (right panel).
© S. Polo/Institut Curie



Comparison between two tumor markers
The presence of CAF-1 or Ki-67, a routinely used tumor marker, is visualized in brown on tissue sections.
In both cases, only the tissues taken from malignant tumors are positively stained. Additionally, statistical analyses show a very good correlation between these two markers, validating CAF-1 as a new proliferation marker.
© Institut Curie

At the Curie Institute in Paris, CNRS researchers have discovered a new proliferation marker : the CAF-1 complex. Since deregulated cell proliferation is one of the most characteristic features of tumor cells, this discovery represents a breakthrough in the cancer field. The researchers from the Curie Institute have already validated the use of this complex as a tumor marker in the context of breast cancer, the most frequent cancer in women.

By combining this marker with other tumor indicators, it will be possible to better characterize tumoral cells and thus to refine diagnosis and develop targeted therapies.
These results are published in the April 1st, 2004 issue of Cancer Research.

Cancer is a disease of the cell. Upon accumulation of genetic alterations, cells proliferate continously, getting out of control by their environment.
The proliferative nature of tumor cells, although harmful to the organism, provides a means of identifying and eliminating them. An example of this is that cellular proliferation is targeted by chemotherapeutic drugs.

It is of major importance to decipher the mechanisms and actors that are involved in tumor cell proliferation to improve cancer diagnosis and treatment.

CAF-1 and cellular proliferation

Cellular proliferation requires DNA replication. Inside the nucleus, DNA, which conveys genetic information, is associated with proteins within a highly organized structure termed chromatin (see the boxed insert). Following its replication, DNA has to be re-assembled into chromatin.

At the Curie Institute, Geneviève Almouzni’s team is interested in factors involved in the assembly of DNA into chromatin. More specifically, they have focused on one particular factor: the CAF-1 complex.

The researchers from the Curie Institute showed that the expression of CAF-1 correlates well with cellular proliferation. Indeed its expression undergoes a massive decrease when cells stop dividing and enter the so-called ‘quiescent’ (non proliferative) state.

Furthermore, the CAF-1 complex is abnormally highly expressed in tumor cells compared to normal ones. This overexpression reflects the excess of cellular proliferation that distinguishes tumors, making CAF-1 a marker of cancer cells.

Thanks to a close collaboration between reseachers and physicians at the Curie Institute, CAF-1 expression could also be analyzed in tumor cells taken from breast cancer patients treated at the Curie Institute. This study, comparing CAF-1 to tumor markers that are used routinely validated CAF-1 as a new proliferation marker in breast cancer, which is the most frequent cancer in women. This new marker, the role of which within the cell is now well determined, opens interesting perspectives for cancer diagnosis and monitoring. Indeed, by combining it with other markers, it will facilitate the monitoring of patients.

Currently research is ongoing to determine the prognostic value of CAF-1 marker in breast cancer and to widen its use to other cancer types.
This work has given rise to applying for a patent.

Chromatin: a complex assembly of DNA and proteins

The DNA, present inside the nucleus of each cell, can be compared to a molecular ribbon, more than one meter long, into which the genetic information is written. Whithin the limited space of a nucleus, DNA is wrapped around proteins to make the highly organized structure chromatin. This compaction of DNA involves a series of specific factors such as CAF-1.

Beyond its structural role, the spatial organization of DNA into chromatin is of major importance for fundamental cellular processes and brings additional informations to those provided by the genetic code.

What are tumor markers ?

Beyond their use as detection tools, tumor markers provide information about tumor cells. Their development will allow :
- diagnosis to be refined,
- better tumor progression predictions,
- monitoring of tumor response to therapies,
- prescription of more specific treatments.

Catherine Goupillon | Source: Institut Curie
Further information: intl-cancerres.aacrjournals.org/

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