Protein expression following γ-irradiation relevant to growth arrest and apoptosis in colon cancer cells

Pfeifer, Daniella; Wallin, Åsa; Holmlund, Birgitta; Sun, Xiao‐Feng

doi:10.1007/s00432-009-0606-4

Cited by 19 publications

(16 citation statements)

References 42 publications

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“…However, AEG-1 knockdown in the cell lines KM12C and HCT116 showed an increased survival. In concordance to previous studies (Pfeifer et al , 2009; Kobunai et al , 2011) these cells had a very high sensitivity to radiation already from start (28% and 33% respectively after 2 Gy). Furthermore, we found in the studied cell lines that high endogenous AEG-1 levels correlated to a high RT sensitivity, but further studies are needed to understand the radiosensitising properties of AEG-1.…”

Section: Discussionsupporting

confidence: 92%

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AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

Gnosa¹,

Zhang

Brodin³

et al. 2014

Br J Cancer

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Background:Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.Methods:The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.Results:The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.Conclusions:The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.

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Section: Discussionsupporting

confidence: 92%

“…We found that AEG-1 knockdown had a radiosensitising effect in the cell lines KM12L4a, SW480, and SW620. Those cell lines are often referred to as radioresistant cells in the literature (Rödel et al , 2005; Pfeifer et al , 2009; Shin et al , 2012). However, AEG-1 knockdown in the cell lines KM12C and HCT116 showed an increased survival.…”

Section: Discussionmentioning

confidence: 99%

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

Gnosa¹,

Zhang

Brodin³

et al. 2014

Br J Cancer

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“…Dosage effects of PTP4A3 expression in relation to cellular responses may be more complex, particularly in cancer cells. For example, in carcinoma cell lines PTP4A3 expression may lead to down regulation of p53 [18] and it is variably induced by γ-irradiation [19]. Finally, high PTP4A3 expression has been linked to increased tumor aggressiveness in different types of solid tumors, e.g., melanoma, gastric cancer, colon cancer, hepatocellular carcinoma and breast cancer [20], [21], [22], [23], [24], possibly because high PTP4A3 expression leads to increased epithelial-mesenchymal transition [25].…”

Section: Discussionmentioning

confidence: 99%

Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

et al. 2011

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Acute myeloid leukemia (AML) results from multiple genetic and epigenetic aberrations, many of which remain unidentified. Frequent loss of large chromosomal regions marks haplo-insufficiency as one of the major mechanisms contributing to leukemogenesis. However, which haplo-insufficient genes (HIGs) are involved in leukemogenesis is largely unknown and powerful experimental strategies aimed at their identification are currently lacking. Here, we present a new approach to discover HIGs, using retroviral integration mutagenesis in mice in which methylated viral integration sites and neighbouring genes were identified. In total we mapped 6 genes which are flanked by methylated viral integration sites (mVIS). Three of these, i.e., Lrmp, Hcls1 and Prkrir, were up regulated and one, i.e., Ptp4a3, was down regulated in the affected tumor. Next, we investigated the role of PTP4A3 in human AML and we show that PTP4A3 expression is a negative prognostic indicator, independent of other prognostic parameters. In conclusion, our novel strategy has identified PTP4A3 to potentially have a role in AML, on one hand as a candidate HIG contributing to leukemogenesis in mice and on the other hand as a prognostic indicator in human AML.

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“…There are well-known short-term and long-term side-effects of pelvic radiation and chemotherapy. Furthermore studies have established that the response to RT is highly individual and that this may partly be explained at the molecular level (5)(6)(7)(8). In order to avoid unnecessary side effects it is important to discover biological factors that could influence recurrence and survival, and to identify patients that will probably not benefit from RT/CRT.…”

Section: Introductionmentioning

confidence: 99%

Response to neoadjuvant treatment in rectal cancer surgery

Loftås

2016

Linköping University Medical Dissertations

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Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT. Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer. Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer. Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour. Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, spe...

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Protein expression following γ-irradiation relevant to growth arrest and apoptosis in colon cancer cells

Abstract: The cell lines seem to have evolved different protein patterns regarding the studied proteins and partly therefore developed different resistance mechanisms, less apoptosis for KM12C and continued proliferation for KM12L4a, after gamma-irradiation.

Cited by 19 publications

References 42 publications

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

Response to neoadjuvant treatment in rectal cancer surgery

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