Article ; Online: HDAC4 Mediates Smoking-Induced Pancreatic Cancer Metastasis.
2022 Volume 51, Issue 2, Page(s) 190–195
Abstract: Objective: Cigarette smoking is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). In this project, we investigated the effect of smoking and the role of histone deacetylase 4 (HDAC4) in PDAC invasion and metastasis.: Methods: ... ...
| Abstract | Objective: Cigarette smoking is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). In this project, we investigated the effect of smoking and the role of histone deacetylase 4 (HDAC4) in PDAC invasion and metastasis. Methods: Cells were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and cigarette smoke extract and the mRNA levels of HDACs were measured by real-time polymerase chain reaction. Invasion was measured using the Matrigel Invasion Assay. Syngeneic PDAC mice were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and metastasis measured. Human PDAC primary and metastatic tissues were analyzed by immunohistochemistry. Results: Levels of HDAC4 mRNA were increased by smoking. Smoking compounds significantly promoted invasion of cancer cells and promoted metastasis of PDAC cells to different organs, including the liver and the lung, whereas inhibition of HDAC4 prevented this effect. The effect of HDAC4 inhibition on preventing smoking-induced metastasis was greater in the liver compared with the lung. We found that HDAC4 is highly expressed in primary and metastatic PDAC tumors. Conclusions: We found that HDAC4 is the only HDAC induced by smoking among all HDACs analyzed. We found that smoking promotes invasion and metastasis of PDAC cells through a mechanism that involves HDAC4 and that HDAC4 is a promising target for preventing PDAC metastasis. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Histone Deacetylases/genetics ; Humans ; Mice ; Neoplasm Metastasis ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; RNA, Messenger ; Repressor Proteins/genetics ; Smoking/adverse effects ; Pancreatic Neoplasms | |||||
| Chemical Substances | RNA, Messenger ; Repressor Proteins ; HDAC4 protein, human (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98) | |||||
| Language | English | |||||
| Publishing date | 2022-04-11 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 632831-3 | |||||
| ISSN | 1536-4828 ; 0885-3177 | |||||
| ISSN (online) | 1536-4828 | |||||
| ISSN | 0885-3177 | |||||
| DOI | 10.1097/MPA.0000000000001998 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 2160: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.