Revealing A Potent Suppressor Of Endometrial Cancer

Endometrial cancer is the most common cancer of the female reproductive tract, representing 6% of all cancers. There is currently no screening method or biomarker to indicate early presence of disease. “It is a very common malignancy that affects women of all ages” comments paper author Dr. Diego Castrillon. The cancer forms from the cells that grow along the inner lining of the uterus, which is called the endometrium, and usually it is diagnosed following patient reports of abnormal bleeding.

The normal endometrium is a dynamic place, providing a thick, highly vascularized environment ready to generate a placenta if it is implanted with an embryo. The dynamic and cyclic activity of the endometrium makes it very sensitive to signaling molecules. Early changes in a number of signaling proteins are known to contribute to endometrial cancer in some patients. A major research goal is to understand how signals create cancer cells and to identify places where intervention might shut down the signals that promote cancer cell survival and growth.

Researchers learn about cancer by creating genetic changes to signaling proteins in mice that reflect changes found in human cancer patients. Animal models are produced in this way to help understand how cancer cells form and progress. One challenge is to localize genetic changes to the environment of interest. In the case of endometrial cancer, researchers need to specifically modify only those cells that are in the endometrium, so that their data is not complicated by changes in other tissues.

In a new study published in Disease Models & Mechanisms (DMM), scientists report a new genetic tool that can specifically alter gene expression in the endometrium. They use this approach to remove a signaling protein gene only in endometrial cells to determine its influence on endometrial cancer formation. They found that the genetic change induced a very rapidly progressing cancer in all mice that carried the mutation. The gene they deleted, called Lkb1, is mutated in many other types of human cancers, and it regulates pathways that are known to contribute to the formation of aggressive cancer cells. Read more

Epigenetic Memory Discovered During Breast Cancer

Researchers from the Boston University School of Medicine (BUSM) have determined how the TGFβ-Smad signaling pathway, which is over activated in late-stage cancers, is responsible for the “epigenetic memory” that maintains unique patterns of regulatory DNA hypermethylation causing silencing of critical genes that facilitate breast cancer progression. The findings, which appear online in Cancer Research, may lead to the development of new therapeutic strategies for late stage breast and other cancers.

According to the researchers, it is becoming increasingly accepted that changes that do not affect the genetic blueprint or DNA sequence, known as the epigenetic landscape, play a major role in defining the properties of normal as well as the cancer cells. While specific epigenetic alterations have been associated with cancer progression, the molecular mediators that ensure transmission of these reversible alterations to successive tumor cells has been elusive.

The BUSM researchers found that the disruption of TGFβ signaling caused a corresponding decrease in the promoter DNA binding activity of DNA methyl transferase 1 leading to passive demethylation of the newly synthesized DNA resulting in expression of genes that are silenced during breast cancer progression. Read more

Genetic Factors Can Increase Leukaemia Risk Seven-Fold

Scientists have found four new regions of the genome that increase the risk of a common blood cancer, according to results published in the journal Nature Genetics.

Professor Richard Houlston and his team at The Institute of Cancer Research (ICR) have now found the location of 10 genetic variants, common in the European population, that are associated with an increased risk of chronic lymphocytic leukaemia (CLL).

Professor Houlston’s team last year proved that people’s genes could make them more susceptible to CLL, identifying six regions of the genome more common among sufferers. In the latest paper, also funded by the charity Leukaemia Research, his team have identified another four regions that influence an individual’s risk of CLL.

CLL is the most common form of leukemiain western countries, with around 2,700 people in the UK diagnosed each year with the disease, most after age 55.

The genetic factors identified in the latest study are all common in the population, and each increases the risk of CLL by between 1.2 and 1.4-fold. Each person may carry from a few of the identified risk factors to all the risk factors. Importantly, the more genetic factors carried, the higher their risk of developing CLL. Read more

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