Differential Expression of Antiapoptotic Genes in Human Endometrial Carcinoma: bcl-XL Succeeds bcl-2 Function in Neoplastic Cells

Crescenzi, Elvira; Criniti, Vittoria; Pianese, Mannida; Tecce, Mario Felice; Palumbo, Giuseppe

doi:10.1006/gyno.2000.5803

Cited by 19 publications

(11 citation statements)

References 14 publications

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“…We found that Bcl‐2 and Bcl‐xL, but not Mcl‐1, XIAP and Bax, basal levels correlated with apoptotic response to cisplatin in all cell lines. Also, the increase in Bcl‐2 content in response to cisplatin in KLE and HEC‐1A further suggested a key role for Bcl‐2 over Bcl‐xL, IAPs and other Bcl‐2 family members in resistance to cisplatin‐induced apoptosis, although previous work enlightened Bcl‐xL as predictor of chemoresistance over Bcl‐2 in endometrial cancer cells 33. Although the implication of Bcl‐xL, Mcl‐1, IAPs, Bax, Bad and PUMA in response to apoptosis induced by cisplatin might be relevant, we hypothesized that Bcl‐2 is the main factor involved in chemoresistance in our condition.…”

Section: Discussionmentioning

confidence: 98%

Cisplatin increases B‐cell‐lymphoma‐2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells

Rouette

Parent

Girouard

et al. 2011

Intl Journal of Cancer

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Human carcinomas often show resistance to cisplatin and Bcl‐2 is associated with resistance to cisplatin. However, Bcl‐2 regulation on cisplatin treatment in human cancers is unknown. Here, we show a novel mechanism by which cisplatin treatment promotes resistance by increasing the expression of Bcl‐2 mRNA. Bcl‐2 mRNA and protein expression was increased in cisplatin‐resistant endometrial cancer cell lines (KLE and HEC‐1‐A), but not in cisplatin‐sensitive cell line (Ishikawa). Cisplatin‐mediated increase in Bcl‐2 expression was blocked by combination with either actinomycin D or cycloheximide. In addition, Bcl‐2 inhibition by HA14‐1 led to increased cisplatin‐induced apoptosis in KLE and HEC‐1‐A, whereas Bcl‐2 overexpression in Ishikawa led to decreased cisplatin‐induced apoptosis. Inhibition of protein kinase C (PKC) activity prevented cisplatin‐dependant increase in Bcl‐2 mRNA, and induced apoptosis in KLE cells. Furthermore, PKC inhibition was associated with decreased Akt and NF‐κB activity. Cells stably expressing shRNA for Akt isoforms revealed that Akt2 was involved in cisplatin‐dependant increase in Bcl‐2 and apoptosis. Overexpression of Akt2 in Akt2‐deficient cells led to increased Bcl‐2 expression on cisplatin treatment. Our data suggest a novel regulation pathway of Bcl‐2 by cisplatin, via the activation of PKC and Akt2, which has a profound impact on resistance to cisplatin‐induced apoptosis in endometrial cancer cells.

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Section: Discussionmentioning

confidence: 98%

Cisplatin increases B‐cell‐lymphoma‐2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells

Rouette

Parent

Girouard

et al. 2011

Intl Journal of Cancer

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“…Deregulation of the biochemical pathways that control physiological cell death can contribute to neoplastic cell expansion by preventing or delaying normal cell death. One of the critical regulators of apoptosis is the protein encoded by the Bcl-2 gene [64,65]. Although the exact biochemical mechanism of Bcl-2 remains enigmatic, the Bcl-2 protein appears to control a distal step in the final common pathway for apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

2010

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AimThe aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.Methods23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.ResultsHistopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (> 2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.ConclusionsOur study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.

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“…HEC1‐B human endometrial carcinoma cells (American Type Cell Culture Collection, ATCC, MD, USA) were cultured as previously described [10]. Their doubling time is >36 h [10]. 1 mg/ml hypericin in dimethylsulfoxide was used as stock solution.…”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction from cells, electrophoresis and protein transfer technique have been described elsewhere [15]. Western immunoblottings and chemiluminescence detection of poly(ADP‐ribose)polymerase (PARP), Bcl‐2, Bax, p21, p53, HSP70, c‐Myc, p‐Bip, VDAC and β‐actin were performed as previously described [9,10,15]. The expression of β‐actin was also used to check protein loading.…”

Section: Methodsmentioning

confidence: 99%

Molecular aspects of photodynamic therapy: low energy pre‐sensitization of hypericin‐loaded human endometrial carcinoma cells enhances photo‐tolerance, alters gene expression and affects the cell cycle

et al. 2002

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Photosensitization of HEC1-B cells with a low concentration of hypericin and doses of light below 10 J/cm 2 caused cell death (apoptosis occurred mainly at doses between 2 and 5 J/cm 2 , whereas necrosis prevailed above 6 J/cm 2 ). However, pre-exposure of cells to innocuous irradiation (2 J/cm 2 ) and successive challenge with a light dose that normally induced apoptosis (5 J/cm 2 ) altered the expression of the proteins involved in the regulation of apoptosis, stress response and cell cycle. This change resulted in a significant increase in cell phototolerance. ß

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Differential Expression of Antiapoptotic Genes in Human Endometrial Carcinoma: bcl-XL Succeeds bcl-2 Function in Neoplastic Cells

Cited by 19 publications

References 14 publications

Cisplatin increases B‐cell‐lymphoma‐2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells

Cisplatin increases B‐cell‐lymphoma‐2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

Molecular aspects of photodynamic therapy: low energy pre‐sensitization of hypericin‐loaded human endometrial carcinoma cells enhances photo‐tolerance, alters gene expression and affects the cell cycle

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