Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice

作者：Xue Ling; Nolla Hector; Suzuki Akira; Mak Tak W^*; Winoto Astar

来源：Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(6): 2022-2027.

DOI：10.1073/pnas.0712059105

• lymphomas
• senescence
• double positive thymocytes
• p27
• cyclin A

PTEN is a tumor suppressor gene but whether cancer can develop in all PTEN-deficient cells is not known. in T cell-specific PTEN-deficient (tPTEN(-/-)) mice, which suffer from mature T cell lymphomas, we found that premalignancy, as defined by elevated AKT and senescence pathways, starts in immature T cell precursors and surprisingly not in mature T cells. Premalignancy only starts in 6-week-old mice and becomes much stronger in 9-week-old mice although PTEN is lost since birth. tPTEN(-/-) immature T cells do not become tumors, and senescence has no role in this model because these cells exist in a novel cell cycle state, expressing proliferating proteins but not proliferiating to any significant degree. instead, the levels of p27(kip1), which is lower in tPTEN(-/-) immature T cells and almost nonexistent in tPTEN(-/-) mature T cells, correlate with the proliferation capability of these cells. interestingly, transient reduction of these cancer precursor cells in adult tPTEN(-/-) mice within a crucial time window significantly delayed lymphomas and mouse lethality. Thus, loss of PTEN alone is not sufficient for cells to become cancerous, therefore other developmental events are necessary for tumor formation.

• 出版日期2008-2-12