Study Hints at Role of Stem Cell Genes in Testicular, Breast Cancers

By Jennifer O'Brien, UCSF News Services | November 29, 2005

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 finding, reported in the November issue of Cancer, suggests that the genes may play a role in the development of tumors or serve as valuable markers of tumor progression, the researchers say. As such, the genes ultimately could lead to new targets for therapy or markers for diagnosis.

A next step, according to the researchers, will be to "dig deeper" 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 researchers focused on seminomas - tumors that account for 50 percent of the cases of testicular cancer, the most frequent cancer in Caucasian males ages 15-40 -- and breast cancers, as represented by a sample of breast cancer cells grown in the culture dish and tissue from a Stage 3 breast tumor.

Previously, the team had discovered that expression of the genes was elevated in two samples of seminomas (Stem Cells, March 2004). In the current study, they expanded their investigation, determining 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. Scientists have known that seminomas arise in sperm-producing germ cells, which are located in the testis and produce sperm in boys following puberty. 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.

Next, turning to cancerous tissue outside of the reproductive system, in this case breast tissue, the team determined, to their surprise, that the expression of the genes was active there, too.

"We thought this was going to be a phenomenon unique to germ cell tumors, says the senior author of the study, Amander Clark, PhD, assistant research geneticist in the laboratory of co-author Renee Reijo Pera, PhD, associate professor of obstetrics, gynecology and reproductive sciences and co-director of the UCSF Human Embryonic Stem Cell Center.

Read more at Jennifer O'Brien, UCSF News Services