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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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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.
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fig1: 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.

Mentions: The presence and the cytoplasmic distribution of BECLIN 1 were first analysed by immunohistochemistry (IHC) in paraffin-embedded tissue sections of ovary carcinomas. BECLIN 1 immunoreactivity in tumour cells presented as a faintly detectable staining diffused in the cytoplasm or as discrete stained puncta (referred to as granular-type) clearly evident in the vicinity of the nucleus. The former immunoreactivity pattern was considered as negative, whereas the latter was considered as positive in terms of BECLIN 1 macroaggregates and indicative of active autophagy. A parallel analysis of BECLIN 1 expression was conducted by immunofluorescence (IF) in the same sections. Results from both techniques overlapped, though some cases judged negative on IHC appeared faintly positive on IF, owing to the highest sensitivity of the latter technique. Representative images of BECLIN 1 expression and cellular distribution, as assessed by IHC and IF in selected cases, are shown in Figures 1 and 2, respectively.


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)

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.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: 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.
Mentions: The presence and the cytoplasmic distribution of BECLIN 1 were first analysed by immunohistochemistry (IHC) in paraffin-embedded tissue sections of ovary carcinomas. BECLIN 1 immunoreactivity in tumour cells presented as a faintly detectable staining diffused in the cytoplasm or as discrete stained puncta (referred to as granular-type) clearly evident in the vicinity of the nucleus. The former immunoreactivity pattern was considered as negative, whereas the latter was considered as positive in terms of BECLIN 1 macroaggregates and indicative of active autophagy. A parallel analysis of BECLIN 1 expression was conducted by immunofluorescence (IF) in the same sections. Results from both techniques overlapped, though some cases judged negative on IHC appeared faintly positive on IF, owing to the highest sensitivity of the latter technique. Representative images of BECLIN 1 expression and cellular distribution, as assessed by IHC and IF in selected cases, are shown in Figures 1 and 2, respectively.

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