羅切斯特大學科學家發(fā)現(xiàn)了裸鼴鼠能夠生存至多28年而不會出現(xiàn)癌癥腫瘤的一種可能的機制。Vera Gorbunova及其同事報告說，這些鼴鼠的不尋常的抗癌特性可能起源于不愿與與鄰居擠在一起的細胞,。
通常，哺乳動物的細胞在相互密切接觸的時候停止復制,，但是癌細胞忽略了這種信號并繼續(xù)增殖,，這讓它們在體內(nèi)聚集成為腫瘤。這組科學家測量了鼴鼠細胞的生長,，并發(fā)現(xiàn)與繼續(xù)生長成為密集層的小鼠細胞相比,，這種鼴鼠的細胞生長對于首次接觸非常敏感。被迫形成高密度狀態(tài)的裸鼴鼠細胞停止了自身的生長,，甚至死亡了,。這組科學家研究了造成這種早期接觸抑制的路徑，并報告說,，兩種成纖維細胞路徑很有可能造成了這種關鍵的抗癌機制,。他們的研究表明，抑制這種腫瘤抑制路徑可以讓這種鼴鼠出現(xiàn)癌癥,。這組作者提出,，裸鼴鼠細胞避免密切接觸的能力可能解釋這種動物的長壽。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS October 26, 2009, doi: 10.1073/pnas.0905252106
Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat
Andrei Seluanova, Christopher Hinea,b, Jorge Azpuruaa, Marina Feigensona,b, Michael Bozzellaa, Zhiyong Maoa, Kenneth C. Cataniac and Vera Gorbunovaa,1
aDepartment of Biology, University of Rochester, Rochester, NY 14627;
bDepartment of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14627; and
cDepartment of Biological Sciences, Vanderbilt University, Nashville, TN 37232
The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed “early contact inhibition.” Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27Kip1. In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16Ink4a. Furthermore, we show that the roles of p16Ink4a and p27Kip1 in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16Ink4a, and regular contact inhibition is controlled by p27Kip1. We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.
