Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma.

Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Research Abstract Details 

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Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Abstract Text:

Lei Xu,Rakesh K Jain,

Two recent clinical trials have shown that the placenta growth factor (PlGF) is up-regulated after bevacizumab treatment in colorectal cancer and after SU11248 treatment in metastatic renal cell carcinoma. The regulation of expression for the vascular endothelial growth factor (VEGF) has been well documented in human tumors; however, the data for PlGF are lacking. We investigated the epigenetic regulation of PlGF and correlated the results with clinicopathologic features. We used plgf promoter analysis, cDNA microarray, immunohistochemistry, and Northern blot analysis to determine the expression level of PlGF in 22 human lung carcinoma and 11 colorectal tumors and in 12 cell lines. Sodium bisulfite modification of genomic DNA followed by methylation-specific PCR (MSP) and sequencing were used to determine the methylation status of the PlGF promoter. Treatments with 5-aza-2'-deoxycytidine and trichostatin A (TSA) were used to reactivate PlGF expression. Significance analysis showed that PlGF expression level was low in human lung and colorectal tumor tissues and in cell lines. PlGF gene promoter was hypermethylated. Treatment with the demethylating agent 5-Aza-dC restored PlGF transcript expression in the lung and colon carcinoma cell lines. By combining the results from cDNA microarray, immunohistochemistry, and MSP, we report, for the first time, that the PlGF gene promoter is methylated, and methylation may be one of the mechanisms that contributes to the low PlGF expression level in human lung and colorectal tumor tissues and cell lines.

Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Publishing Authors By Initials

L Xu,RK Jain,

For similar cells: trophoblasts research abstracts see: cells: trophoblasts research

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Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular cancer research : MCR

VOLUME: 5

Page Numbers: 873-80

Journal Abbreviation: Mol. Cancer Res.

ISSN: 1541-7786

DAY: 17

MONTH: 08

YEAR: 2007

Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Information

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LANGUAGE: eng

NlmUniqueID: 101150042

Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Keywords Mesh Terms:

KEYWORDS: Trophoblasts

MESH TERMS: physiology

Chemical & Substance for Abstract: Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma. Information

Substance Name: product placenta growth factor

Registry Number: 144589-93-5

Grant and Affiliation Information for Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma.

AFFILIATION: Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox-7, Boston, MA 02114, USA. lei@steele.mgh.harvard.edu

Country: United States

AGENCY: United States NCI

GRANT: U01-CA84301

ACRONYM: CA

MEDLINETA: Mol Cancer Res

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