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. 2009 Dec 10:9:430.
doi: 10.1186/1471-2407-9-430.

Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

Min Khine Maw  1 , Jiro Fujimoto, Teruhiko Tamaya
Affiliations

Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

Min Khine Maw et al. BMC Cancer. .

Abstract

Background: The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers.

Methods: Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen.

Results: ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers.

Conclusion: ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers.

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Figures

Figure 1
Figure 1
ID-1, ID-2 and ID-3 mRNA levels in ovarian cancers classified according to clinical stage and histopathological type. Clinical staging of ovarian cancers was done according to FIGO. Each level is the mean ± SD of nine determinations. C, clear cell carcinoma; E, endometrioid adenocarcinoma; MCY, mucinous cystadenocarcinoma; SCY, serous cystadenocarcinoma, SPCY, serous papillary cystadenocarcinoma. Alive and deceased cases are numbered in open circles and closed circles, respectively. * p < 0.001.
Figure 2
Figure 2
Immunohistochemical staining for ID-1 with negative control in ovarian cancers. A representing case of clear cell carcinoma of the ovary. Rabbit anti-human ID-1 (SC-734, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) was used at a dilution of 1:50 as the primary antibody. (original magnification ×400).
Figure 3
Figure 3
Correlation between ID-1 histoscores in cancer cells and mRNA (106 DNA copies/μg total RNA) levels in ovarian cancers. ID-1 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Each level is the mean ± SD of nine determinations.
Figure 4
Figure 4
ID-1 histoscores in ovarian cancers classified according to clinical stage and histopathological type. Clinical staging of ovarian cancers was done according to FIGO. Each level is the mean ± SD of nine determinations. C, clear cell carcinoma; E, endometrioid adenocarcinoma; MCY, mucinous cystadenocarcinoma; SCY, serous cystadenocarcinoma, SPCY, serous papillary cystadenocarcinoma. Alive and deceased cases are numbered in open circles and closed circles, respectively. * p < 0.001.
Figure 5
Figure 5
Survival rate after surgery for ovarian cancers. Patient prognosis was analyzed with a 36-month survival rate. High ID-1, cases with high histoscores and mRNA levels (> 160 histoscore and > 6.2 × 106copies/μg total RNA, respectively). Low ID-1, cases with low histoscores and mRNA levels (< 160 histoscore and < 6.2 × 106 copies/μg total RNA, respectively).
Figure 6
Figure 6
Correlation of ID-1 histoscores in cancer cells and mRNA levels in ovarian cancers with microvessel counts (MVCs). White circles, (MVC-CD34) by immunohistochemical staining for CD34; black circles, (MVC-FV-III) by immunohistochemical staining for factor VIII-related antigen. Each level is the mean ± SD of nine determinations.
See this image and copyright information in PMC

References

    1. Norton JD, Deed RW, Craggs G, Sablitzky F. Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol. 1998;8(2):58–65. doi: 10.1016/S0962-8924(97)01183-5. - DOI - PubMed
    1. Riechmann V, Sablitzky F. Mutually exclusive expression of two dominant-negative helix-loop-helix (dnHLH) genes, Id4 and Id3, in the developing brain of the mouse suggests distinct regulatory roles of these dnHLH proteins during cellular proliferation and differentiation of the nervous system. Cell Growth Differ. 1995;6(7):837–843. - PubMed
    1. Riechmann V, van Cruchten I, Sablitzky F. The expression pattern of Id4, a novel dominant negative helix-loop-helix protein, is distinct from Id1, Id2 and Id3. Nucleic Acids Res. 1994;22(5):749–755. doi: 10.1093/nar/22.5.749. - DOI - PMC - PubMed
    1. Benezra R, Rafii S, Lyden D. The Id proteins and angiogenesis. Oncogene. 2001;20(58):8334–8341. doi: 10.1038/sj.onc.1205160. - DOI - PubMed
    1. Fong S, Debs RJ, Desprez PY. Id genes and proteins as promising targets in cancer therapy. Trends Mol Med. 2004;10(8):387–392. doi: 10.1016/j.molmed.2004.06.008. - DOI - PubMed

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