J Gynecol Oncol.  2008 Sep;19(3):185-190. 10.3802/jgo.2008.19.3.185.

Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues

• Jin KL
• Pak JH
• Park JY
• Choi WH
• Lee JY
• Kim JH
• Nam JH

• KMID: 2173400
• DOI: http://doi.org/10.3802/jgo.2008.19.3.185

Abstract

OBJECTIVE
To investigate the expression levels of histone deacetylase (HDAC) 1, 2, and 3 in ovarian cancer tissues and normal ovarian tissues. METHODS: Randomly assigned each of six patients with serous, mucinous and endometrioid ovarian cancer were included. Another six patients with normal ovarian tissue were included for comparison. RT-PCR was performed to quantify the levels of HDACs1-3 mRNA in the cancer and normal tissues. Western blot analysis was performed to measure the expression levels of HDACs1-3 protein. The HDACs1-3 expression pattern was also topologically examined by immunohistochemistry. RESULTS: Increased mRNA expressions of HDCA1, HDAC 2 and HDAC 3 were detected in 83%, 67% and 83% of 18 cancer tissue samples, compared to normal tissue samples. The relative densities of HDAC1 mRNA and HDAC3 mRNA in the serous, mucinous and endometrioid cancer tissues, and HDAC2 mRNA in serous cancer tissues were significantly higher than those of the normal tissues, respectively (p<0.05). Overexpression of HDAC1, HDAC2 and HDAC3 proteins were detected in 94%, 72% and 83% of 18 cancer samples, respectively. The relative densities of HDAC1 protein and HDAC3 protein in serous, mucinous and endometrioid cancer, and HDAC2 protein in serous and mucinous cancer tissues were significantly higher than those of normal tissues, respectively (p<0.05). Most cancer tissues expressed moderate to strong staining of HDACs1, 2 and 3 in immunohistochemistry. Staining of HDAC2 was weak in only one endometrioid cancer tissue. CONCLUSION: HDACs1-3 are over expressed in ovarian cancer tissues and probably play a significant role in ovarian carcinogenesis.

Keyword

HDAC1; HDAC2; HDAC3; Ovarian cancer

MeSH Terms

Blotting, Western
Histone Deacetylases
Histones
Humans
Immunohistochemistry
Mucins
Ovarian Neoplasms
Proteins
RNA, Messenger
Specific Gravity
Histone Deacetylases
Histones
Mucins
Proteins
RNA, Messenger

Figure

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  Fig. 1 Increased expression of HDAC1, HDAC2 and HDAC3 mRNA in the ovarian cancer tissues, compared with the normal ovarian tissues. (A) Representative RT-PCR analysis of HDACs1, 2 and 3 mRNA from 2 normal and 6 malignant ovarian tissues samples. The membranes were reprobed for β-actin as a loading control. (B), (C) and (D), Relative densitometric values of the data of HDACs1, 2 and 3 mRNA in 6 serous, 6 mucinous, 6 endometrioid cancer tissues and 6 normal tissues. The relative densities of HDAC1 mRNA and HDAC3 mRNA in three kinds of cancer tissues, and HDAC2 mRNA in serous cancer tissues were significantly higher than those in normal tissues. There were no statistically significant differences between HDAC2 mRNA in the mucinous and endometrioid cancer tissues and that in normal tissues (p=0.078 and p=0.109, respectively). Em; endometrioid, Mu; mucinous, Se; serous.

• 

  Fig. 2 Increased expression of HDAC1, HDAC2 and HDAC3 protein in the ovarian cancer tissues, compared with the normal ovarian tissues. (A) Representative Western blots of HDACs 1, 2 and 3 from 2 normal and 6 malignant ovarian tissues samples. The membranes were reprobed for β-actin as a loading control. (B), (C) and (D), Relative densitometric values of the data of HDACs1, 2 and 3 in 6 serous, 6 mucinous and 6 endometrioid cancer tissues and 6 normal tissues. The relative densities of HDAC1 protein and HDAC3 protein in serous, mucinous and endometrioid cancer tissues, and HDAC2 protein in serous and mucinous cancer tissues were significantly higher than those in the normal tissues, respectively (p<0.05). The mean of HDAC2 protein expression was 1.4-fold higher in the endometrioid cancer tissues than that in the normal tissues, but there was no statistically significant difference (p=0.10). Em, endometrioid; Mu, mucinous; Se, serous.

• 

  Fig. 3 Immunohistochemical detection of HDACs1, 2 and 3 in representative samples from 3 normal and 9 malignant ovarian tissues. Most of the tumor samples showed moderate to strong staining, only HDAC2 in the endometrioid tumor tissues showed weak staining. All normal tissues showed weak staining of HDACs1, 2 and 3.

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