Potential Mechanism Identified That May Be Key to Cancer Resistance
听一段采访 博士. 约书亚·希夫曼为您报道
观看视频 博士. Schiffman and the elephants who inspired him
SALT LAKE CITY - Why elephants rarely get 癌症 is a mystery that has stumped scientists for decades. 研究人员领导的一项研究 Huntsman Cancer Institute (HCI) at the University of Utah and Arizona State University, and including researchers from the Ringling Bros. 大象保护中心, may have found the answer.
According to the results, published today in the Journal of the American Medical Association (JAMA), and determined over the course of several years and a unique collaboration between HCI, 初级儿童医院, 犹他州的霍格尔动物园, 还有林林兄弟. 大象保护中心, elephants have 38 additional modified copies (alleles) of a gene that encodes p53, 一种定义明确的肿瘤抑制因子, 与人类相比, 只有两个的人. 进一步, elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming 癌症ous. 在分离的大象细胞中, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime 癌症 risk in children and adults. The results suggest extra p53 could explain elephants' enhanced resistance to 癌症.
"Nature has already figured out how to prevent 癌症. It's up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent 癌症 in people,共同资深作者说 约书亚·希夫曼，m.s.D., pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and 初级儿童医院.
According to Schiffman, elephants have long been considered a walking conundrum. Because they have 100 times as many cells as people, they should be 100 times more likely to have a cell slip into a 癌症ous state and trigger the disease over their long life span of 50 to 70 years. And yet it's believed that elephants get 癌症 less often, a theory confirmed in this study. Analysis of a large database of elephant deaths estimates a 癌症 mortality rate of less than 5 percent compared to 11 to 25 percent in people.
寻找一个解释, the scientists combed through the African elephant genome and found at least 40 copies of genes that code for p53, a protein well known for its 癌症-inhibiting properties. DNA analysis provides clues as to why elephants have so many copies, a substantial increase over the two found in humans. 绝大多数, 其中38个, 是所谓的逆转录酶, modified duplicates that have been churned out over evolutionary time.
Schiffman's team collaborated with 犹他州的霍格尔动物园 and Ringling Bros. 大象保护中心 to test whether the extra gene copies may protect elephants from 癌症. They extracted white blood cells from blood drawn from the animals during routine wellness checks and subjected the cells to treatments that damage DNA, 癌症诱因. 在回应, the cells reacted to damage with a characteristic p53-mediated response: they committed suicide.
“好像大象在说, ‘It's so important that we don't get 癌症, we're going to kill this cell and start over fresh,’”希夫曼说. "If you kill the damaged cell, it's gone, and it can't turn into 癌症. This may be more effective of an approach to 癌症 prevention than trying to stop a mutated cell from dividing and not being able to completely repair itself."
关于癌症, patients with inherited Li-Fraumeni Syndrome are nearly the opposite of elephants. They have just one active copy of p53 and more than a 90 percent lifetime risk for 癌症. Less p53 decreases the DNA damage response in patients with Li-Fraumeni Syndrome, and Schiffman's team wondered if more p53 could protect against 癌症 in elephants by heightening the response to damage. 为了测试这个, the researchers did a side-by-side comparison with cells isolated from elephants (n=8), 健康人（n=10）, and from patients with Li-Fraumeni Syndrome (n=10). They found that elephant cells exposed to radiation self-destruct at twice the rate of healthy human cells and more than five times the rate of Li-Fraumeni cells (14.6%, 7.2%和2.分别为7%). These findings support the idea that more p53 offers additional protection against 癌症.
“通过一切逻辑推理, elephants should be developing a tremendous amount of 癌症, 事实上, should be extinct by now due to such a high risk for 癌症,希夫曼说. "We think that making more p53 is nature's way of keeping this species alive." Additional studies will be needed to determine whether p53 directly protects elephants from 癌症.
"Twenty years ago, we founded the Ringling Bros. 大象保护中心 to preserve the endangered Asian elephant for future generations. Little did we know then that they may hold the key to 癌症 treatment,肯尼斯·菲尔德说, Chairman and CEO of Feld Entertainment.
Read the full story on the Huntsman Cancer Institute website