Abstract |
Hypoxia is a common characteristic of solid tumors. Recent studies confirmed that phospholipase D2 (PLD2) plays significant roles in cancer progression. In this study, correlation between the expression of PLD2 and the change in the protein level of hypoxia-inducible factor 1-alpha (HIF1-α) was studied. Thirty human colon cancer tissues were examined for the expression of HIF1-α and PLD2 protein, and mRNA levels. SW480 and SW620 cells were exposed to normoxia (20 %) or hypoxia (<1 %). HIF1-α and PLD2 protein, and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Growth studies were conducted on cells with HIF1-α inhibition through xenograft tumor model. Finally, PLD2 protein was detected by Western blot analysis in vivo. There was a positive correlation between HIF1-α and PLD2 in colon cancer tissues. Hypoxic stress induced PLD2 mRNA and protein expression in SW480 and SW620 cells. Cells transfected with HIF1-α siRNA showed attenuation of hypoxia stress-induced PLD2 expression. In vivo growth decreased in response to HIF1-α and PLD2 inhibition. These results suggest that PLD2 expression in colon cancer cells is up-regulated via HIF1-α in response to hypoxic stress and underscores the crucial role of HIF1-α-induced PLD2 in tumor growth.
|
Authors | Maoxi Liu, Kunli Du, Zhongxue Fu, Shouru Zhang, Xingye Wu |
Journal | Medical oncology (Northwood, London, England)
(Med Oncol)
Vol. 32
Issue 1
Pg. 394
(Jan 2015)
ISSN: 1559-131X [Electronic] United States |
PMID | 25432699
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- RNA, Small Interfering
- phospholipase D2
- Phospholipase D
|
Topics |
- Adult
- Aged
- Animals
- Blotting, Western
- Cell Hypoxia
(physiology)
- Cell Line, Tumor
- Colonic Neoplasms
(metabolism)
- Female
- Gene Expression Regulation, Neoplastic
(physiology)
- Heterografts
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- Immunohistochemistry
- Male
- Mice
- Mice, Inbred BALB C
- Middle Aged
- Phospholipase D
(biosynthesis)
- RNA, Small Interfering
- Real-Time Polymerase Chain Reaction
- Transfection
- Up-Regulation
|