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TM4SF4 gene

Known as: INTESTINE AND LIVER TETRASPAN MEMBRANE PROTEIN, il-TMP, ILTMP 
National Institutes of Health

Papers overview

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2019
2019
Adopting a proper topology is crucial for transmembrane proteins to perform their functions. We previously reported that ceramide… 
Review
2018
Review
2018
This article has been accepted for publication and undergone full peer review but has not been through the copyediting… 
2017
2017
Substantial evidence has shown that epithelial-mesenchymal transition (EMT) plays critical roles in colorectal cancer (CRC… 
2014
2014
The human thiamine transporter‐2 (hTHTR‐2) is involved in intestinal absorption of thiamine. Recent studies with membrane… 
Review
2014
Review
2014
................................................................................................................................................ 2 RÉSUMÉ ..................................................................................................................................................... 3 ABBREVIATIONS ..................................................................................................................................... 5 TABLE OF CONTENTS ........................................................................................................................... 8 LIST OF FIGURES .................................................................................................................................. 10 LIST OF TABLES .................................................................................................................................... 12 ACKNOWLEDGEMENTS ..................................................................................................................... 13 CONTRIBUTION OF AUTHORS.......................................................................................................... 15 CHAPTER 1: REVIEW OF LITERATURE ......................................................................................... 16 1.1. Classification .................................................................................................................................... 18 1.1.1. Histopathology ....................................................................................................................... 18 1.1.2. Staging ................................................................................................................................... 19 1.1.3. Grading................................................................................................................................... 20 1.1.4. Molecular subtype .................................................................................................................. 20 1.2. Breast tumorigenesis ........................................................................................................................ 23 1.3. Breast cancer metastasis ................................................................................................................... 26 1.3.1. The pre-metastatic niche ........................................................................................................ 31 1.3.2. Liver metastasis ...................................................................................................................... 33 1.4. Metastatic microenvironment ........................................................................................................... 36 1.4.1. Tumor-stroma interactions in the liver microenvironment .................................................... 37 1.5. Rationale and approach .................................................................................................................... 38 CHAPTER 2: MATERIALS AND METHODS .................................................................................... 41 2.1. Cell lines and culture conditions ...................................................................................................... 42 2.2. Antibodies ........................................................................................................................................ 42 2.3. Generation of primary tumors and liver metastases ......................................................................... 42 2.4. Hematoxylin and Eosin staining ...................................................................................................... 43 2.5. Laser capture microdissection of frozen sections ............................................................................ 43 2.6. RNA isolation, amplification, labeling, and hybridization to microarrays ...................................... 44 2.7. Data processing and statistical analysis ........................................................................................... 45 2.8. Immunohistochemistry ..................................................................................................................... 45 2.9. Protein extraction ............................................................................................................................. 46 2.10. Immunoblotting .............................................................................................................................. 46 9 CHAPTER 3: RESULTS ......................................................................................................................... 48 3.1. Generation of murine primary mammary tumors and liver metastases ........................................... 49 3.2. Capturing regions of interest using LCM ......................................................................................... 50 3.3. Quality control and gene expression analysis of microarray data .................................................... 52 3.4. Class comparisons to find differentially expressed genes ................................................................ 53 3.5. Target gene validation: Metastasis core vs. margin comparison ..................................................... 55 3.5.1. Foxm1 ....................................................................................................................................... 56 3.5.2. Dnmt1 ........................................................................................................................................ 57 3.5.3. Brms1 ........................................................................................................................................ 58 3.5.4. Ndrg1 ........................................................................................................................................ 60 3.5.5. Tm4sf4 ...................................................................................................................................... 60 3.6. Gene target validations: Primary tumor vs. liver metastases .......................................................... 60 3.6.1. Lcn2 and S100a8/S100a9 as possible markers of myeloid/granulocytic cell recruitment ........ 61 CHAPTER 4: DISCUSSION AND FUTURE DIRECTIONS .............................................................. 63 4.1. Validation of genes differentially expressed between the core and margin of liver metastases ...... 65 4.2. Class comparisons between primary tumors and liver metastases revealed an enrichment of liver function genes in the metastases ............................................................................................................. 67 4.3. Lcn2 and S100a8 are putative myeloid/granulocytic cell markers .................................................. 70 4.4. Future directions emanating from this work .................................................................................... 74 REFERENCES .......................................................................................................................................... 77 APPENDIX ................................................................................................................................................ 83 
2001
2001
il-TMP (also known as TM4SF4) is a human tetraspanin that is expressed in human intestine and liver. We have cloned a novel cDNA…