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| Name |
| Saleiro, Diana |
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| Nationality |
| Portuguese |
| E-Mail |
| dianasaleiro@gmail.com |
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| 1st Degree |
| Licenciatura: Biology |
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| University (1st Degree) |
| Faculdade de Ciencias da Universidade do Porto |
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| About the PhD |
| Field of Research |
| Cancer Research |
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| Thesis Title |
| MOLECULAR MECHANISMS OF ESTROGEN RECEPTOR BETA ACTION IN COLORECTAL CARCINOGENESIS |
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| Abstract |
| Colorectal cancer (CRC) is a major public health problem in the world population, which emphasizes the need to study novel molecular targets in order to develop alternative chemopreventive and chemotherapeutic strategies... |
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| Colorectal cancer (CRC) is a major public health problem in the world population, which emphasizes the need to study novel molecular targets in order to develop alternative chemopreventive and chemotherapeutic strategies against it. Estrogens have been shown to exert a protective role against CRC and its actions seem to be mediated by estrogen receptor β (ERβ). However, further studies are required to elucidate the role of ERβ in the colon. To achieve this goal, we evaluated the effects of ERβ deficiency in sporadic CRC and colitis-associated CRC (CAC) by using two in vivo models. In addition, we stably transfected RKO colon cancer cells to overexpress ERβ and identify novel molecules regulated by ERβ signaling in vitro. In the sporadic CRC in vivo model, azoxymethane (AOM)-treated ERβ knockout (βERKO) mice showed a significantly higher incidence and multiplicity of colonic preneoplastic lesions compared to AOM-treated ERα knockout and wild-type (WT) mice. These results were associated with a loss of normal colonic crypt organization and a decrease in apoptosis rates suggesting that ERβ is the ER subtype with a protective role against sporadic CRC progression. Confirming this hypothesis, we observed that AOM-treated βERKO mice presented a significantly higher incidence of adenomas than WT mice. By real time-polymerase chain reaction and immunohistochemistry analyses, ERβ-deficient adenomas were shown to be more proliferative and less differentiated than adenomas in WT mice. Furthermore, in the CAC in vivo model, βERKO mice developed more severe clinical colitis compared to WT mice, as evidenced by significantly higher disease activity index, weight to length ratio of the colons, inflammation score, and grade of dysplasia. ERβ-deficient tumors were characterized by a significant increase in pro-inflammatory molecules, suggesting that ERβ might exert anti-inflammatory effects in CAC. Moreover, in vitro results revealed a novel molecular mechanism by which ERβ might drive differentiation of goblet cells in the colonic epithelium. Altogether these findings highlight the importance of ERβ in protection against colorectal carcinogenesis and provide a clinical and translational potential to use ERβ selective agonists in order to prevent and/or treat CRC. |
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| Supervisor(s) |
| Dr. Rajendra G. Mehta |
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| University |
| Illinois Institute of Technology |
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| Laboratory |
| Cancer Biology Division, IIT Research Institute |
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| City |
| Chicago |
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| Country |
| USA |
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| Date of Thesis Defence |
| 2013-07-31 |
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| After the PhD (Current Situation) |
| Position |
| Post-doctoral fellow |
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| Project |
| Definition of cellular signaling pathways regulated by interferon receptors |
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| Institution |
| Northwestern University - Robert H. Lurie Comprehensive Cancer Center |
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| City |
| Chicago |
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| Country |
| USA |
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| Relevant Publications |
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| Saleiro D, Murillo G, Lubahn DB, Kopelovich L, Korach KS, Mehta RG. Enhanced induction of mucin-depleted foci in estrogen receptor {beta} knockout mice. Cancer Prev Res (Phila). 2010;3:1198-204. |
| View Publication |
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Saleiro D, Murillo G, Benya RV, Bissonnette M, Hart J, Mehta RG.
Estrogen receptor-β protects against colitis-associated neoplasia in mice. Int J Cancer. 2012;131:2553-61. doi: 10.1002/ijc.27578.
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| View Publication |
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| Saleiro D, Platanias LC. Intersection of mTOR and STAT signaling in immunity. Trends Immunol. 2015 Jan;36(1):21-9. |
| View Publication |
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| Saleiro D, Mehrotra S, Kroczynska B, Beauchamp EM, Lisowski P, Majchrzak-Kita B, Bhagat TD, Stein BL, McMahon B, Altman JK, Kosciuczuk EM, Baker DP, Jie C, Jafari N, Thompson CB, Levine RL, Fish EN, Verma AK, Platanias LC. Central role of ULK1 in type I interferon signaling. Cell Rep. 2015 Apr 28;11(4):605-17. |
| View Publication |
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| Saleiro D, Kosciuczuk EM, Platanias LC. Beyond autophagy: New roles for ULK1 in immune signaling and interferon responses. Cytokine Growth Factor Rev. 2016 Jun;29:17-22. |
| View Publication |
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| Kosciuczuk EM, Saleiro D, Kroczynska B, Beauchamp EM, Eckerdt F, Blyth GT, Abedin SM, Giles FJ, Altman JK, Platanias LC. Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo. Blood. 2016 Jul 21;128(3):410-4. |
| View Publication |
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| Arslan AD, Sassano A, Saleiro D, Lisowski P, Kosciuczuk EM, Fischietti M, Eckerdt F, Fish EN, Platanias LC. Human SLFN5 is a transcriptional co-repressor of STAT1-mediated interferon responses and promotes the malignant phenotype in glioblastoma. Oncogene. 2017 Jul 3. |
| View Publication |
| Publications |
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| Swarup VP, Huang Y, Murillo G, Saleiro D, Mehta RG, Bishnoi SW. Modeling the cellular impact of nanoshell-based biosensors using mouse alveolar macrophage cultures. Metallomics. 2011 Nov;3(11):1218-26. doi: 10.1039/c1mt00089f. |
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| Mazué F, Delmas D, Murillo G, Saleiro D, Limagne E, Latruffe N. Differential protective effects of red wine polyphenol extracts (RWEs) on colon carcinogenesis. Food Funct. 2014 Apr;5(4):663-70. |
| View Publication |
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| Sakamoto KM, Grant S, Saleiro D, Crispino JD, Hijiya N, Giles F, Platanias LC, Eklund EA. Targeting novel signaling pathways for resistant acute myeloid leukemia. Mol Genet Metab. 2015 Mar;114(3):397-402. |
| View Publication |
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| Colamonici M, Blyth G, Saleiro D, Szilard A, Bliss-Moreau M, Giles FJ, Altman JK, Beauchamp EM, Platanias LC. Dual targeting of acute myeloid leukemia progenitors by catalytic mTOR inhibition and blockade of the p110α subunit of PI3 kinase. Oncotarget. 2015 Apr 10;6(10):8062-70. |
| View Publication |
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| Saleiro D, Platanias LC. ULK1 in type I interferon response. Oncotarget. 2015 Sep 22;6(28):24586-7. |
| View Publication |
[more publications]
| More Publications |
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| Kroczynska B, Rafidi RL, Majchrzak-Kita B, Kosciuczuk EM, Blyth GT, Jemielity J, Warminska Z, Saleiro D, Mehrotra S, Arslan AD, Fish EN, Platanias LC. Interferon γ (IFNγ) Signaling via Mechanistic Target of Rapamycin Complex 2 (mTORC2) and Regulatory Effects in the Generation of Type II Interferon Biological Responses. J Biol Chem. 2016 Jan 29;291(5):2389-96. |
| View Publication |
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| Kosciuczuk EM, Saleiro D, Platanias LC. Dual targeting of eIF4E by blocking MNK and mTOR pathways in leukemia. Cytokine. 2017 Jan;89:116-121. |
| View Publication |
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| Kroczynska B, Blyth GT, Rafidi RL, Majchrzak-Kita B, Xu L, Saleiro D, Kosciuczuk EM, Jemielity J, Su B, Altman JK, Eklund EA, Fish EN, Platanias LC. Central Regulatory Role for SIN1 in Interferon γ (IFNγ) Signaling and Generation of Biological Responses. J Biol Chem. 2017 Mar 17;292(11):4743-4752. |
| View Publication |
| Last Update |
| 2017-10-06 22:21:11 |
| The responsibility for this page contents is entirely of the student/alumnus. |
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Program financially supported by
the National Foundation for
Science and Technology
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