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Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

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Angiopoietin-like protein 2 (ANGPTL2) induces expression of anti-apoptotic BCL-2 family members. (a) Relative mRNA expression of the anti-apoptotic BCL-2 family members BCL-2 (left) and BCL-XL (middle) and of pro-apoptotic BAX (right) in SW480/ANGPTL2-1, SW480/ANGPTL2-2, or SW480/Ctrl cells. Data from SW480/Ctrl was set at 1 (n = 3). (b) BCL-2/BAX and BCL-XL/BAX ratios in SW480/Ctrl, SW480/ANGPTL2-1, or SW480/ANGPTL2-2 cells (n = 3). Error bars show SEM. *P < 0.05; **P < 0.01. n.s., no statistically significant difference.
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fig02: Angiopoietin-like protein 2 (ANGPTL2) induces expression of anti-apoptotic BCL-2 family members. (a) Relative mRNA expression of the anti-apoptotic BCL-2 family members BCL-2 (left) and BCL-XL (middle) and of pro-apoptotic BAX (right) in SW480/ANGPTL2-1, SW480/ANGPTL2-2, or SW480/Ctrl cells. Data from SW480/Ctrl was set at 1 (n = 3). (b) BCL-2/BAX and BCL-XL/BAX ratios in SW480/Ctrl, SW480/ANGPTL2-1, or SW480/ANGPTL2-2 cells (n = 3). Error bars show SEM. *P < 0.05; **P < 0.01. n.s., no statistically significant difference.

Mentions: The BCL-2 family is a key regulator of programmed cell death.(11) It is comprised of both pro- and anti-apoptotic proteins, and the latter (BCL-2, BCL-XL and MCL-1) reportedly inhibit 5-FU-induced apoptosis in CRC cells.(19) Therefore, we examined the expression of BCL-2 family mRNAs in SW480/ANGPTL2-1 and -2 cells or SW480/Ctrl cells. Real-time PCR and Western blot analyses revealed upregulated expression of anti-apoptotic BCL-2 and BCL-XL in SW480/ANGPTL2-1 and -2 cells relative to SW480/Ctrl cells; however, we observed no significant difference in expression of MCL-1 or pro-apoptotic BAX or BAD among groups (Figs 2a,S2). Recently, several reports suggested that a high BCL-2/BAX or BCL-XL/BAX ratio is positively correlated with progression of several diseases or malignant tumors and that the BCL-2/BAX ratio may serve as a prognostic marker for patients with rectal carcinomas.(19,20) Therefore, we analyzed that ratio in SW480/ANGPTL2-1, SW480/ANGPTL2-2, and SW480/Ctrl cells and found that BCL-2/BAX and BCL-XL/BAX ratios were greater in both ANGPTL2-overexpressing lines than they were in controls (Fig. 2b).


Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Angiopoietin-like protein 2 (ANGPTL2) induces expression of anti-apoptotic BCL-2 family members. (a) Relative mRNA expression of the anti-apoptotic BCL-2 family members BCL-2 (left) and BCL-XL (middle) and of pro-apoptotic BAX (right) in SW480/ANGPTL2-1, SW480/ANGPTL2-2, or SW480/Ctrl cells. Data from SW480/Ctrl was set at 1 (n = 3). (b) BCL-2/BAX and BCL-XL/BAX ratios in SW480/Ctrl, SW480/ANGPTL2-1, or SW480/ANGPTL2-2 cells (n = 3). Error bars show SEM. *P < 0.05; **P < 0.01. n.s., no statistically significant difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317964&req=5

fig02: Angiopoietin-like protein 2 (ANGPTL2) induces expression of anti-apoptotic BCL-2 family members. (a) Relative mRNA expression of the anti-apoptotic BCL-2 family members BCL-2 (left) and BCL-XL (middle) and of pro-apoptotic BAX (right) in SW480/ANGPTL2-1, SW480/ANGPTL2-2, or SW480/Ctrl cells. Data from SW480/Ctrl was set at 1 (n = 3). (b) BCL-2/BAX and BCL-XL/BAX ratios in SW480/Ctrl, SW480/ANGPTL2-1, or SW480/ANGPTL2-2 cells (n = 3). Error bars show SEM. *P < 0.05; **P < 0.01. n.s., no statistically significant difference.
Mentions: The BCL-2 family is a key regulator of programmed cell death.(11) It is comprised of both pro- and anti-apoptotic proteins, and the latter (BCL-2, BCL-XL and MCL-1) reportedly inhibit 5-FU-induced apoptosis in CRC cells.(19) Therefore, we examined the expression of BCL-2 family mRNAs in SW480/ANGPTL2-1 and -2 cells or SW480/Ctrl cells. Real-time PCR and Western blot analyses revealed upregulated expression of anti-apoptotic BCL-2 and BCL-XL in SW480/ANGPTL2-1 and -2 cells relative to SW480/Ctrl cells; however, we observed no significant difference in expression of MCL-1 or pro-apoptotic BAX or BAD among groups (Figs 2a,S2). Recently, several reports suggested that a high BCL-2/BAX or BCL-XL/BAX ratio is positively correlated with progression of several diseases or malignant tumors and that the BCL-2/BAX ratio may serve as a prognostic marker for patients with rectal carcinomas.(19,20) Therefore, we analyzed that ratio in SW480/ANGPTL2-1, SW480/ANGPTL2-2, and SW480/Ctrl cells and found that BCL-2/BAX and BCL-XL/BAX ratios were greater in both ANGPTL2-overexpressing lines than they were in controls (Fig. 2b).

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Show MeSH
Related in: MedlinePlus