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.2014:2014:462658.
doi: 10.1155/2014/462658. Epub 2014 Jul 17.

Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer

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Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer

Guido Valente et al. Biomed Res Int.2014.

Abstract

Autophagy is dysregulated in cancer and might be involved in ovarian carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k class III, plays a critical role in the regulation of both autophagy and cell death. Induction of autophagy is associated with the presence of vacuoles characteristically labelled with the protein LC3. We have studied the biological and clinical significance of BECLIN 1 and LC3 in ovary tumours of different histological types. The positive expression of BECLIN 1 was well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of BCL-2. The latter inhibits the autophagy function of BECLIN 1. We found that type I tumours, which are less aggressive than type II, were more frequently expressing high level of BECLIN 1. Of note, tumours of histologic grade III expressed low level of BECLIN 1. Consistently, high level of expression of BECLIN 1 and LC3 in tumours is well correlated with the overall survival of the patients. The present data are compatible with the hypotheses that a low level of autophagy favours cancer progression and that ovary cancer with upregulated autophagy has a less aggressive behaviour and is more responsive to chemotherapy.

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Figures

Figure 1
Figure 1
Immunohistochemical detection of BECLIN 1. Selection of representative cases. The histologic type and the clinical outcome (CR: complete remission; DOD: dead of disease) are indicated. Magnification 220x.
Figure 2
Figure 2
Immunofluorescence detection of BECLIN 1. Selection of representative cases. The histologic type and the clinical outcome (CR: complete remission; DOD: dead of disease) are indicated. The nuclei are evidenced by DAPI staining.
Figure 3
Figure 3
Immunofluorescence staining of LC3 in ovarian cancer tissue sections. Selection of representative cases. The histologic type, the positivity for BECLIN 1 aggregates, the percentage of cells positive for vacuolar LC3, the clinical outcome (CR: complete remission; PR: partial remission; DOD: dead of disease), the pathological stage, and the histologic grade are reported. The nuclei are evidenced by DAPI staining.
Figure 4
Figure 4
Western blotting analysis of the expression of BECLIN 1 and of BCL-2 proteins in ovarian carcinomas. Selection of representative cases. Tissue homogenates were subsequently probed for BECLIN 1, BCL-2, and actin (the latter was used as reference of homogenate protein loading). The molecular weight of proteins detected with the specific antibodies is indicated. Histologic type: S: serous; U: undifferentiated; E: endometrioid.
Figure 5
Figure 5
Immunofluorescence staining of LC3 and BCL-2. Selection of representative cases. The histologic type, the positivity for BECLIN 1 aggregates, the clinical outcome (CR: complete remission; DOD: dead of disease), the pathological stage, and the histologic grade are reported. The nuclei are evidenced by DAPI staining.
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