Sun, 27 Jul 2008 06:19:53 BST CiteULike: carmenv's Zhang http://www.citeulike.org/user/carmenv/author/Zhang CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/carmenv/article/2776585 <i>Molecular carcinogenesis (30 April 2008)</i><br /><br />Considerable evidence has demonstrated that UVB irradiation is a strong carcinogen for nonmelanoma skin cancer. Up-regulation of cyclooxygenase -2 (Cox-2) has been shown to be a crucial event in human keratinocytes in their responses to UVB irradiation. To further understand the molecular mechanisms governing Cox-2 regulation, we found that UVB irradiation significantly increased Cox-2 mRNA stability by inducing cytoplasmic localization and protein abundance of human antigen R (HuR). We also found that AMP-activated kinase (AMPK) mediates these events and that UVB reduces AMPK activity by down-regulating LKB1 kinase. Finally, we propose a novel model in which UVB regulates Cox-2 mRNA stability through the LKB1/AMPK pathway. (c) 2008 Wiley-Liss, Inc. UVB irradiation regulates Cox-2 mRNA stability through AMPK and HuR in human keratinocytes. Jack Zhang G Tim Bowden doi:10.1002/mc.20450 Molecular carcinogenesis (30 April 2008) 2008-05-09T20:34:34-00:00 2008 Molecular carcinogenesis 1098-2744 ampk keratinocytes http://www.citeulike.org/user/carmenv/article/2739313 <i>Blood, Vol. 106, No. 9. (1 November 2005), pp. 3142-3149.</i><br /><br />Shp2 tyrosine phosphatase plays a critical role in hematopoiesis, and dominant active mutations have been detected in the human gene PTPN11, encoding Shp2, in child leukemia patients. We report here that although no such mutations were detected in 44 adult leukemia patients screened, Shp2 expression levels were significantly elevated in primary leukemia cells and leukemia cell lines, as compared with normal hematopoietic progenitor cells. The Shp2 protein amounts correlated well with the hyperproliferative capacity but were inversely associated with the differentiation degree of leukemia cells. Suppression of Shp2 expression induced apoptosis and inhibition of leukemic cell clonogenic growth. Notably, the majority of Shp2 was preferentially localized to the plasma membrane and was constitutively phosphorylated on tyrosine in leukemia cells, and also in normal hematopoietic cells following mitogenic stimulation. Based on these results, we propose that aberrantly increased expression of Shp2 may contribute, collaboratively with other factors, to leukemogenesis. Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia. R Xu Y Yu S Zheng X Zhao Q Dong Z He Y Liang Q Lu Y Fang X Gan X Xu S Zhang Q Dong X Zhang GS Feng doi:10.1182/blood-2004-10-4057 Blood, Vol. 106, No. 9. (1 November 2005), pp. 3142-3149. 2008-04-30T17:47:59-00:00 2005 Blood 0006-4971 106 9 3142 3149 shp2