羅切斯特大學(xué)科學(xué)家發(fā)現(xiàn)了裸鼴鼠能夠生存至多28年而不會(huì)出現(xiàn)癌癥腫瘤的一種可能的機(jī)制。Vera Gorbunova及其同事報(bào)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(xì)胞,。
通常,，哺乳動(dòng)物的細(xì)胞在相互密切接觸的時(shí)候停止復(fù)制,，但是癌細(xì)胞忽略了這種信號(hào)并繼續(xù)增殖,，這讓它們?cè)隗w內(nèi)聚集成為腫瘤。這組科學(xué)家測(cè)量了鼴鼠細(xì)胞的生長(zhǎng),，并發(fā)現(xiàn)與繼續(xù)生長(zhǎng)成為密集層的小鼠細(xì)胞相比,，這種鼴鼠的細(xì)胞生長(zhǎng)對(duì)于首次接觸非常敏感。被迫形成高密度狀態(tài)的裸鼴鼠細(xì)胞停止了自身的生長(zhǎng),，甚至死亡了,。這組科學(xué)家研究了造成這種早期接觸抑制的路徑,，并報(bào)告說,，兩種成纖維細(xì)胞路徑很有可能造成了這種關(guān)鍵的抗癌機(jī)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(xì)胞避免密切接觸的能力可能解釋這種動(dòng)物的長(zhǎng)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.
