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MEK5 overexpression is associated with the occurrence and development of colorectal cancer.

Diao D, Wang L, Wan J, Chen Z, Peng J, Liu H, Chen X, Wang W, Zou L - BMC Cancer (2016)

Bottom Line: Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade.RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells.MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Guangdong Provincal Hospital of Traditional Chinese Medicine, Guangdong, 510120, China. diaodechang@163.com.

ABSTRACT

Background: Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) has been confirmed to play a pivotal role in tumor carcinogenesis and progression. However, few studies have investigated the role of MEK5 in colorectal cancer (CRC).

Methods: MEK5 expression was determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 2 groups of tissues, and western blotting was used to confirm MEK5 expression in 8 cases of primary CRC tissues and paired normal mucosa. RNA interference was used to verify the biological function of MEK5 gene in the development of CRC.

Results: IHC revealed the expression of MEK5 was higher in tumor tissues (38.1 %), compared with adjacent normal tissue (8.3 %). Western blot showed that, MEK5 expression was upregulated in CRC tumor tissues compared with normal tissue. Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade. Survival analysis revealed that MEK5 overexpression negatively correlated with cancer-free survival (hazard ratio 1.64, P = 0.017). RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells.

Conclusion: MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.

No MeSH data available.


Related in: MedlinePlus

Silencing of MEK5 significantly inhibited cancer growth in vivo. a KD cells (5 × 106 in 0.1 ml of PBS) were injected subcutaneously into the left dorsal flank of each BALB/C nude mice, while the same number of BC cells injected subcutaneously into the right dorsal flank. b Tumor mass volume was measured every two days from day 7 to day 21. On day 21 the six mice were sacrificed and all tumors were harvested. c Silencing of MEK5 could significantly inhibited the cancer growth, when compared with BC cells (P < 0.05). d Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells. NC, negative control; KD, knockdown
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Fig6: Silencing of MEK5 significantly inhibited cancer growth in vivo. a KD cells (5 × 106 in 0.1 ml of PBS) were injected subcutaneously into the left dorsal flank of each BALB/C nude mice, while the same number of BC cells injected subcutaneously into the right dorsal flank. b Tumor mass volume was measured every two days from day 7 to day 21. On day 21 the six mice were sacrificed and all tumors were harvested. c Silencing of MEK5 could significantly inhibited the cancer growth, when compared with BC cells (P < 0.05). d Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells. NC, negative control; KD, knockdown

Mentions: To further evaluate the role of reduced MEK5 expression on the tumorigenic phenotype and in particular its contribution to in vivo tumor growth. SW480 cells infected with non-silencing shRNA and MEK5 shRNA were injected into 6 mice, (Fig. 6a). The cancer growth curves in nude mice after injection of MEK5 shRNA transfected cells and the control cells are shown in Fig. 6c. The tumor growth speed of the KD cells was obvious slower than that of NC cells (P < 0.05). These results demonstrate that in vivo tumor growth was inhibited by shRNA-mediated knockdown of MEK5 expression in colon cancer cells. Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells (P < 0.01, Fig. 6d).Fig. 6


MEK5 overexpression is associated with the occurrence and development of colorectal cancer.

Diao D, Wang L, Wan J, Chen Z, Peng J, Liu H, Chen X, Wang W, Zou L - BMC Cancer (2016)

Silencing of MEK5 significantly inhibited cancer growth in vivo. a KD cells (5 × 106 in 0.1 ml of PBS) were injected subcutaneously into the left dorsal flank of each BALB/C nude mice, while the same number of BC cells injected subcutaneously into the right dorsal flank. b Tumor mass volume was measured every two days from day 7 to day 21. On day 21 the six mice were sacrificed and all tumors were harvested. c Silencing of MEK5 could significantly inhibited the cancer growth, when compared with BC cells (P < 0.05). d Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells. NC, negative control; KD, knockdown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4862041&req=5

Fig6: Silencing of MEK5 significantly inhibited cancer growth in vivo. a KD cells (5 × 106 in 0.1 ml of PBS) were injected subcutaneously into the left dorsal flank of each BALB/C nude mice, while the same number of BC cells injected subcutaneously into the right dorsal flank. b Tumor mass volume was measured every two days from day 7 to day 21. On day 21 the six mice were sacrificed and all tumors were harvested. c Silencing of MEK5 could significantly inhibited the cancer growth, when compared with BC cells (P < 0.05). d Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells. NC, negative control; KD, knockdown
Mentions: To further evaluate the role of reduced MEK5 expression on the tumorigenic phenotype and in particular its contribution to in vivo tumor growth. SW480 cells infected with non-silencing shRNA and MEK5 shRNA were injected into 6 mice, (Fig. 6a). The cancer growth curves in nude mice after injection of MEK5 shRNA transfected cells and the control cells are shown in Fig. 6c. The tumor growth speed of the KD cells was obvious slower than that of NC cells (P < 0.05). These results demonstrate that in vivo tumor growth was inhibited by shRNA-mediated knockdown of MEK5 expression in colon cancer cells. Western blot assay showed MEK5 protein expression of the xenograft tumors of KD cells was significantly inhibited comparing with that of NC cells (P < 0.01, Fig. 6d).Fig. 6

Bottom Line: Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade.RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells.MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Guangdong Provincal Hospital of Traditional Chinese Medicine, Guangdong, 510120, China. diaodechang@163.com.

ABSTRACT

Background: Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) has been confirmed to play a pivotal role in tumor carcinogenesis and progression. However, few studies have investigated the role of MEK5 in colorectal cancer (CRC).

Methods: MEK5 expression was determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 2 groups of tissues, and western blotting was used to confirm MEK5 expression in 8 cases of primary CRC tissues and paired normal mucosa. RNA interference was used to verify the biological function of MEK5 gene in the development of CRC.

Results: IHC revealed the expression of MEK5 was higher in tumor tissues (38.1 %), compared with adjacent normal tissue (8.3 %). Western blot showed that, MEK5 expression was upregulated in CRC tumor tissues compared with normal tissue. Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade. Survival analysis revealed that MEK5 overexpression negatively correlated with cancer-free survival (hazard ratio 1.64, P = 0.017). RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells.

Conclusion: MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.

No MeSH data available.


Related in: MedlinePlus