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EZH2 Cancer Markers

a cancer marker and ezh2 technology, applied in the field of ezh2 cancer markers, can solve the problems of lack of prostate cancer sensitivity and specificity of serum psa tests, and the impact of psa screening on cancer-specific mortality is still unknown

Inactive Publication Date: 2009-01-08
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0003]The present invention relates to therapeutic targets for cancer. In particular, the present invention relates ...

Problems solved by technology

However, the impact of PSA screening on cancer-specific mortality is still unknown pending the results of prospective randomized screening studies (Etzioni et al., J. Natl. Cancer Inst., 91:1033 ; Maattanen et al., Br. J. Cancer 79:1210 ; Schroder et al., J. Natl. Cancer Inst., 90:1817 ).
A major limitation of the serum PSA test is a lack of prostate cancer sensitivity and specificity especially in the intermediate range of PSA detection (4-10 ng / ml).

Method used

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Examples

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example 1

miRNA Inhibition of EZH2 Expression

A. Experimental Approach

[0158]The primary structure of precursor miR-101 is shown in FIG. 1. FIG. 1 shows the sequence database entry for mir-101 from Sanger's Registry. The cartoon depicts the predicted stem-loop hairpin. miR-101 is predicted to target the 3′ UTR of EZH2 at 2 independent sites and both predictions are the top ranked hits from the Sanger Registry.

[0159]The functional consequences of perturbing miR-101 levels in cells was evaluated. Expression of EZH2 protein was measured by immunoblot analysis. Invasion assays were carried out as previously described (Kleer et al., supra) and pre-miR-101 was transfected along with siRNA against EZH2 (as a positive control) and luciferase siRNA (as a negative control) as well as several unrelated miRs.

B. Results It was assessed whether miR-101 regulates EZH2 expression in cell lines. Upon transfection of the precursor miR-101 in SKBr3 breast cancer cells a marked decrease in EZH2 protein expression ...

example 2

Small Molecule Inhibition of EZH2

[0161]In order to understand the mechanism of EZH2 mediated invasion, cDNA expression microarray analysis was performed using the RNA isolated from EZH2 overexpressing cells along with control RNA (FIG. 4A). It was observed that the tumor suppressor protein E-cadherin was specifically downregulated. These observations were further confirmed by immunoblot assays as well as coimmunostainings (FIG. 4 B, C). Furthermore, the inverse correlation between increased EZH2 expression and E-cadherin down regulation was observed in aggressive breast tumors as well. The studies showed that the oncogenic function of EZH2 works by activating a pro-invasion program through transcriptional repression of E-cadherin among other factors.

A. Experimental Approach

[0162]A high throughput screening protocol was used to identify small molecule inhibitors of EZH2. Primary breast cancer cells were transfected with the E-cadherin promoter luciferase reporter gene and infected wi...

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Abstract

The present invention relates to therapeutic targets for cancer. In particular, the present invention relates to small molecules and nucleic acids that target EZH2 expression in prostate cancer.

Description

[0001]This application claims priority to provisional patent application Ser. No. 60 / 958,151, filed Jul. 3, 2007, which is herein incorporated by reference in its entirety.[0002]This invention was made with government support under CA97063 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates to therapeutic targets for cancer. In particular, the present invention relates to small molecules and nucleic acids that target EZH2 expression in cancer (e.g., prostate cancer and other solid tumors).BACKGROUND OF THE INVENTION[0004]Afflicting one out of nine men over age 65, prostate cancer (PCA) is a leading cause of male cancer-related death, second only to lung cancer (Abate-Shen and Shen, Genes Dev 14:2410 [2000]; Ruijter et al, Endocr Rev, 20:22 [1999]). The American Cancer Society estimates that about 184,500 American men will be diagnosed with prostate cancer and 39,200 will die in 200...

Claims

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Application Information

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IPC IPC(8): A61K31/7105C12N5/06A61P31/00A61K31/35
CPCA61K31/35A61P31/00
Inventor CHINNAIYAN, ARUL M.LNU, SOORYANARAYANACAO, QI
Owner RGT UNIV OF MICHIGAN
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