Importância dos Saca-Rabos (Herpestes Ichneumon) como Reservatório de Mycobacterium avium subsp. paratuberculosis. Deteção por Técnicas Tradicionais e Moleculares

Poster apresentado nas IV Jornadas de Genética, realizadas na UTAD, Vila Real, nos dias 1,2 e 3 de Março de 2012.Os saca-rabos (Herpestes ichneumon) também conhecidos por mangustos, são carnívoros diurnos selvagens que juntamente com a geneta (Genetta genetta) representam os exemplares da família Viverridae em Portugal. É uma espécie cinegética de caça menor que se alimenta de coelhos, roedores, aves, cobras, insectos e ovos. Neste estudo colheram-se amostras de 8 animais mortos por atropelamento e em ações de controlo de predadores, durante os anos de 2010 e 2011, nos concelhos de Idanha-a-Nova e Penamacor do distrito de Castelo Branco. As amostras colhidas foram fígado, pulmão, baço, intestino, rim, gânglio mesentérico, retrofaríngeo, mediastínico, amígdalas e fezes. As amostras foram submetidas à técnica de PCR e a cultura microbiológica em meios específicos. Em três saca-rabos (37,5%) detectou-se Mycobacterium avium subsp. paratuberculosis (Map) através da técnica de biologia molecular. Dois eram machos e um era fêmea. Map foi confirmado também em cultura nos dois machos. Sete saca-rabos (87,5%) apresentaram bactérias álcool-ácido resistentes compatíveis com Map em esfregaços de diferentes tecidos, quando corados pelo método de Ziehl-Neelsen. Estes resultados preliminares confirmam os saca-rabos como reservatório de Map no nosso país. Atualmente, estão a ser desenvolvidos mais estudos para a avaliação dos saca-rabos na dinâmica da infeção de Map em mamíferos selvagens

K-Ras-Activated Cells Can Develop into Lung Tumors When Runx3-Mediated Tumor Suppressor Pathways Are Abrogated

10.14348/molcells.2020.0182MOLECULES AND CELLS4310889-89

RUNX3 regulates cell cycle-dependent chromatin dynamics by functioning as a pioneer factor of the restriction-point

The transcription factor RUNX3 plays a key role in the restriction point of cell cycle. Here the authors showed that RUNX3 binds and opens chromatin structure of restriction point associated genes, by sequential recruitment of chromatin remodeling complex, transcription complex and cell cycle regulators

Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/- mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/- bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3-/- epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+/- mice (similar to 18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Runx3+/- mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma. Oncogene (2010) 29, 3349-3361; doi:10.1038/onc.2010.79; published online 15 March 2010Chi XZ, 2009, CANCER RES, V69, P8111, DOI 10.1158/0008-5472.CAN-09-1057Ito K, 2009, ONCOGENE, V28, P1379, DOI 10.1038/onc.2008.496Ito T, 2008, ASIAN ECON POLICY R, V3, P237, DOI 10.1111/j.1748-3131.2008.00107.xDovey JS, 2008, P NATL ACAD SCI USA, V105, P11857, DOI 10.1073/pnas.0803574105Peacock CD, 2008, J CLIN ONCOL, V26, P2883, DOI 10.1200/JCO.2007.15.2702Licchesi JDF, 2008, CARCINOGENESIS, V29, P895, DOI 10.1093/carcin/bgn017Collins LG, 2007, AM FAM PHYSICIAN, V75, P56Weisenberger DJ, 2006, NAT GENET, V38, P787, DOI 10.1038/ng1834Lau QC, 2006, CANCER RES, V66, P6512, DOI 10.1158/0008-5472.CAN-06-0369Yano T, 2006, MOL CELL BIOL, V26, P4474, DOI 10.1128/MCB.01926-05Cardoso WV, 2006, DEVELOPMENT, V133, P1611, DOI 10.1242/dev.02310Wistuba II, 2006, ANNU REV PATHOL-MECH, V1, P331, DOI 10.1146/annurev.pathol.1.110304.100103Sato K, 2006, ONCOL REP, V15, P129Kim WJ, 2005, CANCER RES, V65, P9347, DOI 10.1158/0008-5472.CAN-05-1647Ito K, 2005, CANCER RES, V65, P7743, DOI 10.1158/0008-5472.CAN-05-0743Chi XZ, 2005, MOL CELL BIOL, V25, P8097, DOI 10.1128/MCB.25.18.8097-8107.2005Kim CFB, 2005, CELL, V121, P823, DOI 10.1016/j.cell.2005.03.032Goel A, 2004, INT J CANCER, V112, P754, DOI 10.1002/ijc.20472Tozawa T, 2004, CANCER SCI, V95, P736Valk-Lingbeek ME, 2004, CELL, V118, P409Tuveson DA, 2004, CANCER CELL, V5, P375Reddy R, 2004, AM J PHYSIOL-LUNG C, V286, pL658, DOI 10.1152/ajplung.00159.2003Leung C, 2004, NATURE, V428, P337, DOI 10.1038/nature02385Fainaru O, 2004, EMBO J, V23, P969, DOI 10.1038/sj.emboj.7600085Kang GH, 2004, J PATHOL, V202, P233, DOI 10.1002/path.1503Bishop AE, 2004, CELL PROLIFERAT, V37, P89Xiao WH, 2004, WORLD J GASTROENTERO, V10, P376Li QL, 2004, BIOCHEM BIOPH RES CO, V314, P223, DOI 10.1016/j.bbrc.2003.12.079Kato N, 2003, AM J PATHOL, V163, P387Woolf E, 2003, P NATL ACAD SCI USA, V100, P7731Guo WH, 2002, ONCOGENE, V21, P8351, DOI 10.1038/sj.onc.1206037Taniuchi I, 2002, MOL CELL, V10, P1083Inoue K, 2002, NAT NEUROSCI, V5, P946, DOI 10.1038/nn925Dimri GP, 2002, CANCER RES, V62, P4736Levanon D, 2002, EMBO J, V21, P3454Li QL, 2002, CELL, V109, P113Lund AH, 2002, CANCER CELL, V1, P213Minna JD, 2002, CANCER CELL, V1, P49Jackson EL, 2001, GENE DEV, V15, P3243Bangsow C, 2001, GENE, V279, P221Osanai M, 2001, ULTRASTRUCT PATHOL, V25, P367Vonlanthen S, 2001, BRIT J CANCER, V84, P1372Bea S, 2001, CANCER RES, V61, P2409Petersen I, 2001, ANAL CELL PATHOL, V22, P111COSTA RH, 2001, AM J PHYSIOL-LUNG C, V280, P823ZOCHBAUERMULLER S, 2000, CHEST SURG CLIN N AM, V10, P691Mori M, 1998, ULTRASTRUCT PATHOL, V22, P459Belinsky SA, 1998, P NATL ACAD SCI USA, V95, P11891Malkinson AM, 1998, EXP LUNG RES, V24, P541Cazorla M, 1998, MOL CARCINOGEN, V21, P251Look AT, 1997, SCIENCE, V278, P1059Lee B, 1997, NAT GENET, V16, P307Otto F, 1997, CELL, V89, P765Mundlos S, 1997, FASEB J, V11, P125Westra WH, 1996, CANCER RES, V56, P2224Wuenschell CW, 1996, J HISTOCHEM CYTOCHEM, V44, P113OKUDA T, 1996, MOL DIAGN, V1, P1391

Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm*

RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers