The viral gene v-Src is an oncogene, a type of gene that has the potential to cause cancer. It was the first oncogene ever discovered, a finding that revealed the disease could be caused by specific, identifiable genes. Found within the genome of a virus, v-Src’s identification provided a model that helped scientists understand the genetic basis of cancer.
The Discovery of v-Src
The story of v-Src begins in the early 20th century. In 1911, pathologist Peyton Rous was studying a sarcoma, a type of connective tissue cancer, in a hen. Rous conducted experiments where he took tumor samples, ground them up, and passed them through a filter fine enough to remove any cells or bacteria. When he injected this cell-free fluid into healthy chickens, they developed the same cancerous tumors.
This experiment demonstrated that a non-cellular agent could transmit cancer. This agent was later identified as a virus and named the Rous sarcoma virus (RSV). For decades, this finding was met with skepticism, but it laid the groundwork for future investigation. Rous was eventually awarded the Nobel Prize in 1966 for his discovery.
The next major breakthrough came in the 1970s from the work of J. Michael Bishop and Harold Varmus. They sought to identify the precise component within the Rous sarcoma virus responsible for its cancer-causing ability. Their research proved that a single gene within the virus, which they named v-Src (for viral sarcoma), was the culprit.
The Cellular Counterpart c-Src
The identification of v-Src led Bishop and Varmus to another discovery. They developed a molecular probe specific to the v-Src gene and used it to search the DNA of normal, uninfected chicken cells. They found a nearly identical gene was already present in the chickens’ own genetic material. This finding demonstrated that the cancer-causing gene was not foreign but a captured and altered version of a normal cellular gene.
This normal gene was named c-Src (for cellular Src) and was subsequently found in the DNA of all vertebrates, including humans. The existence of c-Src revealed that our cells carry genes that, if mutated or improperly activated, could contribute to cancer.
The c-Src protein functions as a non-receptor tyrosine kinase, an enzyme that acts as a molecular switch for many cellular processes. It participates in regulating cell growth, division, differentiation, and movement. Its activity is tightly controlled, ensuring that cells only divide and migrate when appropriate, such as during embryonic development or tissue repair.
How v-Src Causes Cancer
The difference between the harmless c-Src and the cancer-causing v-Src lies in its regulation. The v-Src gene is a mutated version of the c-Src gene, and these mutations cause the resulting protein to be perpetually active. The normal c-Src protein has a built-in “off switch,” a region at its end called the C-terminal regulatory tail. When this tail is chemically modified, it folds back and locks the protein in an inactive state.
In the v-Src protein, this entire regulatory tail is missing. Without this inhibitory region, the v-Src protein cannot be turned off and is permanently stuck in the “on” position. This condition is analogous to a car’s gas pedal being welded to the floor, leading to constant, unchecked acceleration.
Because v-Src is always active, it continuously sends powerful signals that command the cell to grow and divide without stopping. This relentless signaling drives the uncontrolled proliferation that is characteristic of cancer. The constant activity of v-Src also disrupts the cell’s internal scaffolding and interferes with molecules that help cells stick to one another. These changes cause cancer cells to lose their normal shape, detach from the primary tumor, and become mobile, allowing them to invade surrounding tissues and metastasize.
The Broader Impact on Cancer Research
The discovery of v-Src and c-Src introduced and solidified the concepts of “oncogenes” and “proto-oncogenes.” A proto-oncogene is a normal gene like c-Src that can become a cancer-causing oncogene like v-Src if it acquires mutations. This genetic view of cancer opened up entirely new avenues for treatment.
The realization that a single, hyperactive enzyme could drive a cell to become cancerous suggested that blocking that specific enzyme could be an effective therapy. This idea gave rise to the field of targeted cancer therapy, which focuses on developing drugs that inhibit the specific proteins driving a patient’s cancer.
The first successful drugs based on this concept were kinase inhibitors, molecules designed to block the activity of enzymes like Src. While early Src-specific inhibitors showed limited success as single agents, the principle they established was sound. The development of other kinase inhibitors has led to some of the most effective treatments in modern oncology, transforming patient outcomes in several types of leukemia, lung cancer, and breast cancer.