UCSF scientists have discovered that the activity of several embryonic stem cell genes is elevated in testicular and breast cancers, providing some of the first molecular evidence of a link between embryonic stem cells and cancer.

The genes may play a role in the development of tumors or serve as valuable markers of tumor progression, the researchers say. The genes may ultimately be able to lead to new targets for therapy or markers for diagnosis.

Researchers are trying to determine the functions of the genes in the cells that make up the tumors. Another step will be to explore whether the genes are expressed in other cancers, such as prostate cancer.

The genes are known as OCT 4, NANOG, STELLAR and GDF3.

The focus is mainly on seminomas, tumors that account for 50 percent of the cases of testicular cancer, and breast cancer.

Previously, the team had discovered that expression of the genes was elevated in two samples of seminomas. In the recent study, the research was expanded, and it was found that the expression of the genes was elevated, at varying levels, in nine seminomas.

In the process, they identified the window during which seminomas begin to develop. Germ cells, like all cells of the body, develop from embryonic stem cells, and go through a multi-stage evolution in their structure and genetic activity before attaining their mature state. The study revealed that the genetic misregulation leading to seminomas begins very early in the formation of sperm-producing germ cells.

The team found that in case of breast tissue expression of genes was active outside the reproductive system.

This is the first indication that these genes are markers of breast cancer. This finding might help in knowing the origin of breast cancer.

The current study evolved from ongoing research in the Reijo Pera lab is aimed at identifying the genes that lead human embryonic stem cells to evolve into early-stage germ cells, and ultimately to specialize as sperm-producing cells or eggs, or oocytes. The goal of this research is to identify the genetic missteps that lead to birth defects and infertility.

The current study demonstrated that the four genes had elevated expressions in the nine seminoma samples examined, when compared with normal testis tissue. GDF3 was elevated in 90 percent of cases, OCT4 was elevated in 56 percent of cases and NANOG and STELLAR expression were elevated in 33 percent of cases.

The team also examined the relative expression of these genes, and four other genes that play an important role in normal testis, in the nine samples. OCT 4 and NANOG were the highest expressed genes in each of the seminoma samples.

Finally, they examined breast cancer tissue and normal breast tissue. While normal tissue did not express detectable levels of the genes, both the breast carcinoma cell lines and stage 3 breast carcinoma expressed all four genes.

The scientists suspect that expression of the genes may be elevated in other non-reproductive cancers, as well, such as those of the prostate. Studies have shown, says Clark, co-director of UCSF Human Embryonic Stem Cell Center, that OCT 4, which works with NANOG to regulate the capacity of cells to specialize, causes dysplatic lesions in the intestines, skin and stomach. It would be useful to look at NANOG in those places where we know over expression of OCT 4 results in tumor progression, she says. It may be playing a role there, too.

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