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Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas

The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed u...

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Autores principales: KATAGIRI, HIROSHI, NAKAYAMA, KENTARO, RAZIA, SULTANA, NAKAMURA, KOHEI, SATO, EMI, ISHIBASHI, TOMOKA, ISHIKAWA, MASAKO, IIDA, KOUJI, ISHIKAWA, NORIYOSHI, OTSUKI, YOSHIRO, NAKAYAMA, SATORU, KYO, SATORU
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665333/
https://www.ncbi.nlm.nih.gov/pubmed/26458502
http://dx.doi.org/10.3892/ijo.2015.3191
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author KATAGIRI, HIROSHI
NAKAYAMA, KENTARO
RAZIA, SULTANA
NAKAMURA, KOHEI
SATO, EMI
ISHIBASHI, TOMOKA
ISHIKAWA, MASAKO
IIDA, KOUJI
ISHIKAWA, NORIYOSHI
OTSUKI, YOSHIRO
NAKAYAMA, SATORU
KYO, SATORU
author_facet KATAGIRI, HIROSHI
NAKAYAMA, KENTARO
RAZIA, SULTANA
NAKAMURA, KOHEI
SATO, EMI
ISHIBASHI, TOMOKA
ISHIKAWA, MASAKO
IIDA, KOUJI
ISHIKAWA, NORIYOSHI
OTSUKI, YOSHIRO
NAKAYAMA, SATORU
KYO, SATORU
author_sort KATAGIRI, HIROSHI
collection PubMed
description The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquine or Beclin 1 siRNA did not enhance the sensitivity of the ES2 and TOV-21G OCCC cell lines to CDDP. Loss of Beclin 1 expression was observed in 38.3% (23/60) of the analyzed tumors. There was no significant correlation between loss of Beclin 1 expression and FIGO stage, CA125 levels, patient age, status of endometriosis, Ki-67 labeling index, chemotherapy regimen or status of residual tumor. However, negative expression of Beclin 1 was associated with a shorter progression-free survival in comparison to positive Beclin 1 expression in OCCC who received cytoreductive surgery, followed by a standard platinum-based chemotherapy regimen (P=0.027, log-rank test). Beclin 1-negative tumors were no more resistant to primary adjuvant chemotherapy than were Beclin 1-positive tumors (50.0 vs. 66.7%, P=0.937). Beclin 1 knockdown using siRNA increased cell growth but not cell migration and invasion in ES2 and TOV-21G OCCC cell lines. Autophagy defects caused by loss of Beclin 1 are not related to chemoresistance and metastasis, but may be associated with malignant phenotype and poor prognosis of OCCC.
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spelling pubmed-46653332015-12-04 Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas KATAGIRI, HIROSHI NAKAYAMA, KENTARO RAZIA, SULTANA NAKAMURA, KOHEI SATO, EMI ISHIBASHI, TOMOKA ISHIKAWA, MASAKO IIDA, KOUJI ISHIKAWA, NORIYOSHI OTSUKI, YOSHIRO NAKAYAMA, SATORU KYO, SATORU Int J Oncol Articles The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquine or Beclin 1 siRNA did not enhance the sensitivity of the ES2 and TOV-21G OCCC cell lines to CDDP. Loss of Beclin 1 expression was observed in 38.3% (23/60) of the analyzed tumors. There was no significant correlation between loss of Beclin 1 expression and FIGO stage, CA125 levels, patient age, status of endometriosis, Ki-67 labeling index, chemotherapy regimen or status of residual tumor. However, negative expression of Beclin 1 was associated with a shorter progression-free survival in comparison to positive Beclin 1 expression in OCCC who received cytoreductive surgery, followed by a standard platinum-based chemotherapy regimen (P=0.027, log-rank test). Beclin 1-negative tumors were no more resistant to primary adjuvant chemotherapy than were Beclin 1-positive tumors (50.0 vs. 66.7%, P=0.937). Beclin 1 knockdown using siRNA increased cell growth but not cell migration and invasion in ES2 and TOV-21G OCCC cell lines. Autophagy defects caused by loss of Beclin 1 are not related to chemoresistance and metastasis, but may be associated with malignant phenotype and poor prognosis of OCCC. D.A. Spandidos 2015-10-06 /pmc/articles/PMC4665333/ /pubmed/26458502 http://dx.doi.org/10.3892/ijo.2015.3191 Text en Copyright: © Katagiri et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
KATAGIRI, HIROSHI
NAKAYAMA, KENTARO
RAZIA, SULTANA
NAKAMURA, KOHEI
SATO, EMI
ISHIBASHI, TOMOKA
ISHIKAWA, MASAKO
IIDA, KOUJI
ISHIKAWA, NORIYOSHI
OTSUKI, YOSHIRO
NAKAYAMA, SATORU
KYO, SATORU
Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title_full Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title_fullStr Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title_full_unstemmed Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title_short Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas
title_sort loss of autophagy-related protein beclin 1 may define poor prognosis in ovarian clear cell carcinomas
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665333/
https://www.ncbi.nlm.nih.gov/pubmed/26458502
http://dx.doi.org/10.3892/ijo.2015.3191
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