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

Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C - Biomed Res Int (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Anatomy Pathology, Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.

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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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.
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fig3: 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.

Mentions: In autophagy active cells, the microtubule-associated LC3 protein is posttranslationally translocated into the membranes of autophagosomes [8]. Therefore, the detection of a granular-like staining of LC3 can be assumed bona fide as the proof of the presence of autophagic vacuoles (either autophagosomes or autophagolysosomes) in the cell. We analysed by immunofluorescence the expression of LC3 in selected BECLIN 1-positive (n = 30) and BECLIN 1-negative cases (n = 12). Cells were considered positive for ongoing autophagy when showing a granular-like staining for LC3 and the tumour was considered autophagy-active when ≥20% of the cells were LC3 positive. Examples of LC3 staining in BECLIN 1-positive tumour cells are shown in Figure 3. With a few exceptions, cases judged positive for BECLIN 1 were highly positive also for LC3. On the whole, we found a concordance of 70% between the expression of both BECLIN 1 and LC3.


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

Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C - Biomed Res Int (2014)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127242&req=5

fig3: 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.
Mentions: In autophagy active cells, the microtubule-associated LC3 protein is posttranslationally translocated into the membranes of autophagosomes [8]. Therefore, the detection of a granular-like staining of LC3 can be assumed bona fide as the proof of the presence of autophagic vacuoles (either autophagosomes or autophagolysosomes) in the cell. We analysed by immunofluorescence the expression of LC3 in selected BECLIN 1-positive (n = 30) and BECLIN 1-negative cases (n = 12). Cells were considered positive for ongoing autophagy when showing a granular-like staining for LC3 and the tumour was considered autophagy-active when ≥20% of the cells were LC3 positive. Examples of LC3 staining in BECLIN 1-positive tumour cells are shown in Figure 3. With a few exceptions, cases judged positive for BECLIN 1 were highly positive also for LC3. On the whole, we found a concordance of 70% between the expression of both BECLIN 1 and LC3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Anatomy Pathology, Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.

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.

Show MeSH
Related in: MedlinePlus