Expression of BDNF, TrkB, and p53 in early-stage squamous cell carcinoma of the uterine cervix

Moon, Ahrim; Won, Kyu Yeoun; Lee, Jung Yeon; Kang, In‐Cheol; Lee, Sun-Kyung; Lee, Juhie

doi:10.1097/pat.0b013e3283484a3a

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…BDNF has been found to mediate protection from apoptosis by p53 activation (18). High expression of BDNF and its receptor TrkB have been found in cancers related to metastasis and poor prognosis, in addition p53 is related in the late process of tumor progression and predict of a poor prognosis in squamous cell carcinoma of the uterine cervix (4,19).…”

Section: Discussionmentioning

confidence: 99%

Biological influence of brain-derived neurotrophic factor on breast cancer cells

Yang

Martin

Jiang

2012

International Journal of Oncology

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Abstract. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily which has been indicated in the pathophysiology of the nervous system and is important in a number of neurological and psychological conditions. Recently, BDNF was also shown to play a role in the development and progression of solid tumour myeloma. It has been reported that BDNF is aberrantly expressed in human breast cancer and that a raised level of BDNF is associated with poor clinical outcome and reduced survival. The present study investigated the role of BDNF in human breast cancer. A panel of human breast cancer cells was used and the expression profile of BDNF was evaluated using RT-PCR. We constructed a set of anti-BDNF transgenes which were used to transfect breast cancer cells in order to generate BDNF knocked down cells. The impact of BDNF knockdown on growth and apoptosis was evaluated. Statistical analysis was performed using SPSS. P<0.05 was considered statistically significant. BDNF gene transcripts were successfully detected in the breast cancer cell lines MCF-7, MDA-MB-231 and ZR75-1 MDA-MB-231 and MCF-7 wild-type cells were subject to transfection of anti-BDNF transgenes, followed by the establishment of BDNF knocked down sublines. Knockdown of BDNF in MDA-MB-231 and MCF-7 cell lines resulted in decreased rates of growth and proliferation.Analysis of apoptosis showed that cell apoptosis was increased in cells stably transfected with ribozymes for BDNF compared with the vector control. It is concluded that BDNF, a neurotrophic growth factor aberrantly expressed in cancers such as breast cancer, has a profound impact on the cellular behaviour of breast cancer cells and that BDNF is associated with a reduction of the apoptosis of breast cancer. BDNF is, therefore, a potential therapeutic target in breast cancer and its effect in human breast cancer requires further investigation. IntroductionThe incidence of breast cancer continues to rise. Breast cancer is one of the common carcinoma in women. The treatment of breast cancer includes routine surgery, radiotherapy, biotherapy and hormone therapy. These treatments have shortcomings due to side effects and lack of response due to the different genetic makeup of the individual and their disposition to breast cancer. Recently, there has been a move towards an individual treatment regime. The search therefore continues to find markers and/ or targets for therapy (1,2). Brain-derived neurotrophic factor, BDNF is a member of the neurotrophins superfamily composed of 247 amino acids which has separated and purified from pig brain (3). BDNF activates cellular biological effects mainly through a cell surface tyrosine kinase receptor, tropo-myosinrelated kinase B (TrkB). It has been reported that brain-derived neurotrophic factor (BDNF) is aberrantly expressed in human breast cancer and that a raised level of BDNF is associated with poor clinical outcome and reduced survival (4,5). BDNF is secreted by target non-neuronal cells of neuron and has been implicated in ...

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Section: Discussionmentioning

confidence: 99%

Biological influence of brain-derived neurotrophic factor on breast cancer cells

Yang

Martin

Jiang

2012

International Journal of Oncology

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“…BDNF expression was shown to be higher in breast cancer samples compared with normal tissue, and higher levels of BDNF transcripts were significantly associated with unfavorable pathological parameters and adverse clinical outcomes including poor prognosis and death from breast cancer [14]. The expression of BDNF and TrkB mRNA was also higher in human cervical cancer cell lines and squamous cell carcinoma of the uterine cervix than in normal tissues, and was related to clinicopathological parameters related to early-stage squamous cell carcinoma [15]. Other solid tumors in which TrkB expression is elevated and might be associated with a poorer disease outcome include Wilm's tumor, ovarian cancer and pancreatic ductal adenocarcinoma (reviewed in [4]).…”

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confidence: 91%

BDNF/TrkB signaling as an anti-tumor target

Roesler¹,

Farias

Abujamra

et al. 2011

Expert Review of Anticancer Therapy

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“…BDNF/TrkB promote cancer cell survival and resistance to chemotherapy, while small-molecule inhibitors of Trk, such as K252α, inhibit cell growth and induce apoptotic death in cancer cells (16)(17)(18)(19). TrkB expression has been described in ovarian and cervical cancers (20,21), while being associated with a shorter survival and the promotion of metastasis in ovarian cancer patients (20 in cell proliferation, migration and suppression of anoikis (22,23). In breast cancer, BDNF expression has been shown to be higher in tumor samples compared to non-neoplastic tissues, while BDNF transcript levels have been associated with unfavorable pathological parameters and adverse clinical outcomes (24).…”

Section: Introductionmentioning

confidence: 99%

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

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Abstract. Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.

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Expression of BDNF, TrkB, and p53 in early-stage squamous cell carcinoma of the uterine cervix

Cited by 24 publications

References 38 publications

Biological influence of brain-derived neurotrophic factor on breast cancer cells

Biological influence of brain-derived neurotrophic factor on breast cancer cells

BDNF/TrkB signaling as an anti-tumor target

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

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