O papel dos C/EBPs no estômago. Diferenciação vs proliferação. José Carlos Machado, Porto, Portugal.

Slides:

Advertisements

Similar presentations

Introduction to Oncology Dr. Saleh Unit 9 R.E.B, 4MedStudents.com 2003.

Advertisements

Comparison of Mutations and Protein Expression in Potentially Actionable Targets in 5500 Triple Negative vs. non-Triple Negative Breast Cancers Joyce A.

BMP Receptor 1 : Juvenile Polyposis (Colon Cancer) Cecily Johnson Biology 169 March 24, 2005.

SMAD4/DPC4: A Tumor Suppressor James Brooks March 23 rd, 2006.

Cell Identity Determined by types and amounts of proteins in the cell

Theories of cancer genesis

Nadia Dubé *, Alan Cheng * and Michel L. Tremblay * McGill Cancer Centre and Department of Biochemistry, McGill University, 3655 Promenade Sir-William-Osler,

Transforming Growth Factor-Beta Receptor 2 TGF-β receptor 2

Tumor Supressor Gene Non-functional TSG Mutations increasing risk of cancer “Loss of function” mutation Proto-oncogene Oncogene (Hyperactive or unregulated.

Vecchi e nuovi “targets”, vecchi e nuovi farmaci

Apoptosis (Programmed Cell Death). Apoptosis vs Necrosis Level of stress, change in environment stress apoptosisnecrosis.

Advanced Cancer Topics Journal Review 4/16/2009 AD.

Sef Inhibits Fibroblast Growth Factor Signaling by Inhibiting FGFR1 Tyrosine Phosphorylation and Subsequent ERK Activation Authors: Dmitry Kovalenko, Xuehoi.

MiR-19b/20a/92a regulates the self- renewal and proliferation of gastric cancer stem cells Journal of Cell Science (IF=5.325) 报告人：黄美玲

Kyoto University, Japan

Gene Transcription G0G0 G1G1 Priming S G2G2 M Cell Cell Cycle Growth Factors + Growth Factors & Cell Cycle Receptors.

Β-Catenin, Cancer, and G Proteins Not Just for Frizzleds Anymore Ming Yang et al. PNAS Maria Domenica Castellone et al. Science

Computational biology of cancer cell pathways Modelling of cancer cell function and response to therapy.

Functions of Onc-Gene Products: Growth Factor Receptors Signal Transduction, Nuclear Transcription Factors Folder Title: OncProteins Updated: April 20,

Premalignant states n Tubular GI Tract: 1. Esophagus – Barrett’s epithelium 1. Esophagus – Barrett’s epithelium 2. Stomach – dysplasia, IM due to 2. Stomach.

Fernando Cotait Maluf Diretor do Departamento de Oncologia Clínica Centro de Oncologia-Hospital São José Fernando Cotait Maluf Diretor.

BRG-1 in Cancer BRG-1 is an ATPase subunit of the SWI/SNF class of chromatin remodeling complexes It has been found mutated in a number of cancer cell.

Germline polymorphisms in the CD44 gene are associated with clinical outcome in localized gastric adenocarcinoma. Thomas Winder, M.D. University of Southern.

Additional File 1 A. p38 (38 kDa) shRNA Control p53 (53 kDa) shRNA p53 B. Untransfected cells Relative cell no. GFP- vector GFP-Ras G12V Fluorescence Additional.

Aberrant Wnt /  -catenin signaling can induce chromosomal instability in colon cancer Behrens. J et al, PNAS, 2006.

Oesophagus. Oesophagus - squamous cell carcinoma Multiple LOH Amplification of CMYC, EGFR, CYCLIN D1, HST1… Overexpression of Cyclin D1 LOH at 3p2; LOH.

Chromatin remodelling ATPase Brg-1 is an essential factor for the maintenance of the intestinal crypt stem cell and adenoma formation Aliaksei Holik.

Types of Genes Associated with Cancer

Biology of Cancer Weeks 1 Introduction and 2 RTKs Dr. Michael Chorney Susquehanna Medicine and Health Science Magnet February 17 th -28 th, 2014.

Vijay Kumar, Ph.D. Scientist, Virology Group International Centre for Genetic Engg. and Biotechnology (ICGEB) New Delhi, India Virology-2015,

Integrin-EGFR Cross-Activation Elizabeth Brooks Department of Chemical Engineering University of Massachusetts, Amherst Peyton Lab Group Meeting December.

Relative ratio PC(16:0/16:1) (  M) p-Akt Akt PC(16:0/16:1) (  M) kDa p-Erk Erk PC(16:0/16:1) (  M) /44 kDa Relative.

The expression and signaling of FGFR3 in WM cells.

Training Set Clinicopathological parameters of the training set

WNT5A is a Key Regulator of the Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties in Human Gastric Carcinoma Cells Pathobiology 2013;80:

Cell Physiol Biochem 2017;44:1867– DOI: /

Over-Expression of HER2 Causes Cancer: A Mathematical Model

Epidermal Growth Factor Promotes Proliferation and Migration of Follicular Outer Root Sheath Cells via Wnt/β-Catenin Signaling Cell Physiol Biochem 2016;39:

Concept 18.5: Cancer results from genetic changes that affect cell cycle control The gene regulation systems that go wrong during cancer are the very same.

Matteo Centonze, Concetta Saponaro, Anita Mangia

Volume 19, Issue 5, Pages (May 2011)

The Role of Myc A Master Regulator Gone Awry

Figure 3 The cell cycle and the role of CDK4/6 inhibition

IHC analyses of levels and/or phosphorylation status of selected proteins from representative sections of ventral prostate of Hi-Myc mice. IHC analyses.

The Role of MSH2 in Hereditary Non-Polyposis Colon Cancer

Zara E Khan, Timothy C Wang, Guanglin Cui, Alfred L Chi, Rod Dimaline

Volume 131, Issue 4, Pages (October 2006)

Volume 143, Issue 3, Pages (September 2012)

PTEN Tumor Suppressor and Cancer

Keratinocyte Apoptosis in Epidermal Development and Disease

Ganglioside GM3 Promotes Carcinoma Cell Proliferation via Urokinase Plasminogen Activator-Induced Extracellular Signal-Regulated Kinase-Independent p70S6.

Volume 81, Issue 3, Pages (February 2012)

Microarray analysis of phospho-Twist1–responsive genes.

Volume 74, Issue 11, Pages (December 2008)

Inflammation, Atrophy, Gastric Cancer: Connecting the Molecular Dots

M.B.Ch.B, MSC, PhD, DCH (UK), MRCPCH

Volume 138, Issue 4, Pages (April 2010)

Nat. Rev. Clin. Oncol. doi: /nrclinonc

Integrin-β4–TNS4–Focal Adhesion Kinase Signaling Mediates Keratinocyte Proliferation in Human Skin Eun Young Seo, Seon-Pil Jin, Yeon Kyung Kim, Hanon.

Mechanism of Akt1 in promoting reprogramming.

C/EBPα induces HSD1 expression and is a substrate of USP2–45.

OPCML-associated RTK modulation affects downstream signaling.

Down-regulation of the erbB-2 receptor by trastuzumab decreases Akt kinase activation but not MAPK activation. Down-regulation of the erbB-2 receptor by.

A, Proportion of variants detected in the MMR genes.

EGFR signaling regulates transcription of PDGFRβ gene.

LY elicits hyperphosphorylation of Akt.

Skp2, the FoxO1 hunter Cancer Cell

Presentation transcript:

O papel dos C/EBPs no estômago. Diferenciação vs proliferação. José Carlos Machado, Porto, Portugal

Aneuploidy # 3p, 7q, 13q (LOH) # 6q (LOH) # 1q, 5q, 17p (LOH) RAS (overexpression/mutation) ERBB-2 (amplification) TPR-MET (rearrangement) c-MET (6.0 Kb mARN) p 53 (LOH, mutation) APC (LOH, mutation) DCC (LOH) EGF (overexpression) TGF-a (overexpression) TFF1 (loss of expression) MSI (Microsatellite Instability) S-Tn, T, S-T CDw75, S-Lex Laminin, collagen IV u-PA, Cat-D NM 23 (loss) CD 44 (variants) Diploidy # 3p, 7q, 13q (LOH) # 6q (LOH) c-MET (6.0 Kb mRNA) p 53 (LOH, mutation) TGF-ß (overexpression) K-SAM (amplification) E-cadherin (loss/mutation) S-Tn, T, S-T CDw75, S-Lex NM 23 (loss) CD 44 (variants) Intestinal carcinoma Diffuse carcinoma

Gastric gland

TFF1 expression in gastric carcinogenesis. Machado JC et al. J Pathol 190: 437, 2000

C/EBPbeta Ki67 Ki67 and C/EBP-β in normal gastric mucosa

Intestinal metaplasiaGastric dysplasia C/EBPbeta expression

Intestinalatypicaldiffuse IntestinalSolid Diffuse C/EBPbeta expression

C/EBP-β staining overlaps Ki67 C/EBPKi67

C/EBPbeta mutation in a primary gastric carcinoma Pro58Ala Wild-type

Basic leucine zipper DNA-binding protein C/EBP-β or NFIL6

TFF1 knockout mice developed adenomas and gastric cancer Lefebvre O et al. Science 274: 259, 1996

C/EBPbeta and COX-2 co-expression in gastric carcinoma COX2C/EBPbetaDouble IHC

C/EBP-β expression in GC cell lines

Luciferase assay showing the effect of C/EBPbeta transfection on COX-2 promoter activity

C/EBPα is expressed in gastric differentiated cells and co-localizes with TFF1

C/EBPα is under expressed in 34.6% of intestinal and atypical but not diffuse type carcinomas non-neoplasticintestinaldiffuse

A C/EBPα expression vector inhibits AGS cell proliferation BRDU Dapi média Mock42KD isoformas % proliferação média

C/EBPα modulates cell cycle proteins and is capable of up-regulating TFF1 expression

EGFR HER2/neu IL6R/GP130 TGFBR STAT3 Pi3K Ras SHP2 GSK3beta ERK C/EBPbeta Smad3 phosphorylation inactivation AKT TFF1 COX2 Candidate signalling pathways

C/EBPβ C/EBPα ciclinD1 p-ERK1/2 p-p38 tubulin C/EBP  stimulation with IL1B leads to phosphoeilation of ERK1/2 and p38 0 SBPD IL1b IL1b+ SB- p38 IL1b+ PD ERK

phospho-p38 C/EBP β Ki67 C/EBP  co-localizes with phopho-p38

Conclusions C/EBPbeta is expressed in proliferative cells of the normal gastric mucosa, and is overexpressed in intestinal metaplasia, dysplasia, and GC of the intestinal and atypical subtypes; COX-2 is co-expressed with C/EBPbeta and can be regulated by this transcription factor; C/EBPbeta may both be a marker of neoplastic transformation and play an active role in gastric tumourigenesis by regulating COX-2 expression; C/EBPα is expressed in gastric foveolar differentiated cells and under-expressed in intestinal and atypical type tumours; C/EBPα colocalizes with and up-regulates TFF1, and inhibits cell proliferation by changing the expression of cell cycle proteins in vitro.