The role of MAP kinases and MAP kinase phosphatase-1 in resistance to breast cancer treatment

Haagenson, Kelly K.; Wu, Gen Sheng

doi:10.1007/s10555-010-9208-5

Cited by 90 publications

(77 citation statements)

References 39 publications

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“…The MAPK signaling pathways are important in cell growth, drug resistance and malignant transformation in various tumor types (17)(18)(19). Understanding the molecular mechanism behind the sporamin-induced MAPK activation should benefit the development of novel therapies for PC.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of ERK1/2, which is associated with proliferative and anti-apoptotic responses, resulted in the generation of resistance to chemotherapeutic drugs in PC cells (21). Increased MAPK activation following chemotherapeutic drug treatments is indicative of a potential increase in the abundance of MAPKs (17)(18)(19)(20)(21). In the present study, it was demonstrated that sporamin induced the activation of ERK1/2, JNK1/2 and p38 in a concentration-dependent manner, and that MAPK inhibitors attenuated this effect of sporamin in PANC-1 cells.…”

Section: Discussionmentioning

confidence: 99%

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Mitogen‑activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells

Qian

Zhong

et al. 2018

Oncol Lett

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Abstract. Sporamin, a sweet potato tuber storage protein, is a Kunitz-type trypsin inhibitor (TI) that has exhibited antitumor activity through poorly defined mechanisms in a number of types of tumor cells. The present study aimed to analyze the combined effects of sporamin and three mitogen-activated protein kinase (MAPK) inhibitors, PD98059, SP600125 and SB203580, on the pancreatic cancer cell line, PANC-1. Cell proliferation activity was assessed using a 3 H-thymidine incorporation assay, and cell viability was analyzed using an MTT assay. Apoptosis was assayed by flow cytometry and fluorescence microscopy. Protein expression levels in PANC-1 cells were determined by western blotting. The results of this analysis demonstrated that sporamin induced a temporary increase in the phosphorylation of MAPKs, including phosphorylated extracellular signal regulated-kinase 1/2, phosphorylated c-Jun amino-terminal protein kinase 1/2 and phosphorylated p38-MAPK, in a concentration-dependent manner. However, treatment with MAPK inhibitors promoted the inhibition of cell proliferation and viability, and the induction of apoptosis in sporamin-treated PANC-1 cells.In conclusion, the present study demonstrated that MAPK inhibition enhanced the antitumor activity of sporamin in PANC-1 cells. IntroductionPancreatic cancer (PC) is among the most aggressive types of solid tumor, and has the highest rate of cancer-associated mortality worldwide (1). Despite advances in surgical techniques, chemotherapy and radiotherapy, the long-term survival rate for patients with PC has not significantly increased since 1977 (2). Therefore, further research into alternative therapies for PC, which has fewer associated toxicities, is urgently required.Trypsin inhibitors (TIs) are widely distributed in plants and animals, and certain types of TIs have exhibited antitumor activity in several types of tumor cells (3-5). Although no approved therapies directly targeting trypsin directly are currently available, development of novel and more specific TI therapies is underway (3-5). Sporamin, a sweet potato tuber storage protein, is a Kunitz-type TI that has been demonstrated to induce antitumor effects in vitro and in vivo (4,5). Although the role and mechanism of sporamin as an antitumor agent remain unclear, the previous research has indicated that sporamin can mediate the regulation of specific signaling pathways (5). For example, sporamin was demonstrated to inhibit cell growth and induce apoptosis of human tongue cancer cells by downregulating RAC serine/threonine-protein kinase/glycogen synthase kinase-3 signaling (5). However, to the best of our knowledge, the antitumor effects of sporamin in PC have not been previously investigated.Mitogen-activated protein kinases (MAPK) are critically involved in the signaling cascades that govern various critical processes, including cell proliferation, differentiation, apoptosis and survival (6). MAPKs are conserved enzymes that connect cell-surface receptors to their regulatory targets within cells (7). Th...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitogen‑activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells

Qian

Zhong

et al. 2018

Oncol Lett

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“…In 2009, 209,060 new cases of breast cancer were diagnosed, and 40,230 deaths occurred from breast cancer in the United States (2). One of the important problems confronted during the course of breast cancer treatment is resistance to chemotherapy (3). Accumulating evidence indicates that the expression of several growth factor receptors, including the epidermal growth factor receptor (4), human epidermal growth factor receptor type 2 (HER2) (5), and insulin-like growth factor-1 receptor (6), is often elevated in chemotherapy-resistant breast tumors.…”

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confidence: 99%

Phosphorylation of Caspase-7 by p21-activated Protein Kinase (PAK) 2 Inhibits Chemotherapeutic Drug-induced Apoptosis of Breast Cancer Cell Lines

Wen

Liu

et al. 2011

Journal of Biological Chemistry

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p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in resistance to chemotherapy is unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with a human non-tumorigenic mammary epithelial cell line and adjacent normal breast tissue, respectively. Interestingly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at the Ser-30, Thr-173, and Ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapeutic resistance in human breast invasive ductal carcinoma by negatively regulating caspase-7 activity.

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“…In breast cancer, KRAS/MAPK signaling has an important role in transfer growth signaling from the extracellular environment (37,38). The activation of the KRAS/MAPK signaling pathway induces numerous responses in breast cancer cells, resulting in the regulation of cell proliferation, differentiation, migration and invasion (39).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-134 targets KRAS to suppress breast cancer cell proliferation, migration and invasion

Zhang

et al. 2017

Oncology Letters

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Abstract. The expression patterns and functions of microRNA-134 (miR-134) have been previously studied in numerous types of cancer. To the best of our knowledge, this is the first study of miR-134 in human breast cancer. In the present study, the expression patterns, biological functions and underlying molecular mechanisms of miR-134 in human breast cancer were investigated. Reverse transcription-quantitative polymerase chain reaction evaluated the expression of miR-134 in human breast cancer tissues, matched normal adjacent tissues, breast cancer cell lines and a normal mammary epithelial cell line. Following transfection with miR-134, an MTT assay, cell migration assay, cell invasion assay, western blot analysis and a luciferase assay were performed on the MCF-7 and MDA-MB-231 human breast cancer cell lines. The findings revealed that miR-134 expression levels were significantly downregulated in breast cancer cells. Statistical analysis demonstrated that low expression of miR-134 was significantly associated with lymph node metastasis, TNM stage and reduced cell differentiation. It was observed that miR-134 inhibited the growth, migration and invasion of breast cancer cells. Additionally, the present study indicated that miR-134 may directly target the Kirsten rat sarcoma viral oncogene homolog in breast cancer tissues. These results suggest that miR-134 may be used as a potential therapeutic biomarker in breast cancers.

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The role of MAP kinases and MAP kinase phosphatase-1 in resistance to breast cancer treatment

Cited by 90 publications

References 39 publications

Mitogen‑activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells

Mitogen‑activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells

Phosphorylation of Caspase-7 by p21-activated Protein Kinase (PAK) 2 Inhibits Chemotherapeutic Drug-induced Apoptosis of Breast Cancer Cell Lines

MicroRNA-134 targets KRAS to suppress breast cancer cell proliferation, migration and invasion

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