Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells.

Abstract

AIM:

Protein L-isoaspartyl O-methyltransferase (PIMT) regulates cell adhesion in various cancer cell lines through activation of integrin αv and the PI3K pathway. The epithelial mesenchymal transition (EMT) enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow them to migrate for metastasis. Here, we examined the relationship between PIMT and EMT with attached or detached MDA-MB 231 cells.

METHODS:

Human breast cancer cell line MDA-MB-231 cells were maintained in a suspension on poly-HEMA in the presence or absence of PIMT siRNA or ERK inhibitor PD98059. The mRNAs and proteins were analyzed using RT-PCR and immunoblotting, respectively.

RESULTS:

During cellular incubation under detached conditions, PIMT, integrin αv and EMT proteins, such as Snail, Slug and matrix metalloproteinase 2 (MMP-2), were significantly increased in correlation with the phosphorylation of ERK1/2. The ERK inhibitor PD98059 (25 μmol/L) strongly suppressed the expression of the proteins and PIMT. Interestingly, PIMT siRNA blocked the phosphorylation of ERK and the expression of the EMT proteins. Additionally, PIMT and ERK phosphorylation were both co-activated by treatment with TGF-β (10 ng/mL) and TNF-α (10 ng/mL).

CONCLUSION:

A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the EMT.

• Authors: Jiyeon Ryu, Jihyeok Song, Jieun Heo, Yongwoo Jung, Sang-Jin Lee, Sungyoul Hong, Jae Youl Cho
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 32 Issue 9 Pg. 1165-72 (Sep 2011) ISSN: 1745-7254 [Electronic] United States
• PMID: 21841813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Organic Cation Transport Proteins
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• solute carrier family 22 (organic cation transporter), member 3
• Protein D-Aspartate-L-Isoaspartate Methyltransferase
• Extracellular Signal-Regulated MAP Kinases

Topics

• Breast Neoplasms (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Organic Cation Transport Proteins (genetics)
• Protein D-Aspartate-L-Isoaspartate Methyltransferase (genetics, metabolism)
• Transforming Growth Factor beta (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)