The gene appears to influence the growth of extra nipples, but is also thought to be involved in breast cancer. Its identification promises to bring new insights into the causes and treatment of the disease.
Researchers at the Breakthrough Breast Cancer Centre at the Institute of Cancer Research have called the gene after the fiendish character Scaramanga, played by Christopher Lee in the 1974 James Bond film The Man with the Golden Gun. Bond’s adversary was identifiable only by his third nipple.
Professor Alan Ashworth and his team had wanted to understand the trigger for breast development, including what controls the number of mammary glands. They found that Scaramanga helps to determine how and where breast tissue is laid down while the embryo is developing, in addition to the number of breasts that form. They report their finding in Genes and Development.
In embryo development the formation of all organs and tissues is tightly controlled by different genes. In humans the process normally results in two breasts, but the process sometimes goes awry.
“Identifying the Scaramanga gene is a real advance in our understanding of the early steps in breast formation,” Professor Ashworth said. “By learning more about this gene and the protein it produces, it will allow us to determine how normal breast development is initiated, and, importantly, examine how this is connected with breast cancer.
Scaramanga was identified in mice strains known to have abnormal breast development and is one of several genes involved in the pathway to breast formation. The gene product, a protein called Neuregulin3 (NRG3), is a growth-stimulating substance which signals cells to become breast cells. Although the link with extra nipples has been made only in mice at this stage, “it is likely to be involved in humans”, Professor Ashworth says.
The protein is very similar to proteins found in breast cancer, suggesting a direct link between the two. NRG3 activates cells that have a protein very similar to one over-expressed in about 20 per cent of breast cancers and which can be targeted by the drug Herceptin.
“While proteins carefully control the development of breast cells in the embryo, inappropriate signals to breast cells during adulthood by these same molecules may cause breast cancer,” Professor Ashworth said.
Third nipples are not very rare: one in eighteen people has one. They can range in appearance from a small mole-like structure to a full breast, which may lactate, even in men. Third nipples are more common in men than in women.
Men have nipples because their physiological structure is laid down during embryo development before the genetic “male” signal is switched on.
The occurrence of third nipples has been observed since Roman times and are often attributed to increased femininity and fertility. In Salem, however, women with third nipples were condemned as witches and burnt at the stake, as they were thought to use them to suckle the Devil. Anne Boleyn, the second wife of King Henry VIII, was victimised because of her third nipple.
These days, self-help websites provide tips on how to use third nipples advantageously in dating, socialising and, bizarrely, career advancement. There are even websites devoted to people’s third nipple piercings.
People who have third nipples are not thought to be at greater risk of contracting breast cancer, although the tissue area should regularly be checked for lumps.
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