罗切斯特大学科学家发现了裸鼹鼠能够生存至多28年而不会出现癌症肿瘤的一种可能的机制。Vera Gorbunova及其同事报告说，这些鼹鼠的不寻常的抗癌特性可能起源于不愿与与邻居挤在一起的细胞。
通常，哺乳动物的细胞在相互密切接触的时候停止复制，但是癌细胞忽略了这种信号并继续增殖，这让它们在体内聚集成为肿瘤。这组科学家测量了鼹鼠细胞的生长，并发现与继续生长成为密集层的小鼠细胞相比，这种鼹鼠的细胞生长对于首次接触非常敏感。被迫形成高密度状态的裸鼹鼠细胞停止了自身的生长，甚至死亡了。这组科学家研究了造成这种早期接触抑制的路径，并报告说，两种成纤维细胞路径很有可能造成了这种关键的抗癌机制。他们的研究表明，抑制这种肿瘤抑制路径可以让这种鼹鼠出现癌症。这组作者提出，裸鼹鼠细胞避免密切接触的能力可能解释这种动物的长寿。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
