Mortalin promotes ovarian cancer cell growth through MAPK-ERK signal pathway

HU Ying-ying HAN Yan-yan ZHAO Jia-wei YANG Ling LIU Wen ZUO Ji*

Acta Anatomica Sinica ›› 2014, Vol. 45 ›› Issue (3) : 338-343.

Welcome to visit Acta Anatomica Sinica! Today is Chinese
Acta Anatomica Sinica ›› 2014, Vol. 45 ›› Issue (3) : 338-343. DOI: 10.3969/j.issn.0529-1356.2014.03.008

Mortalin promotes ovarian cancer cell growth through MAPK-ERK signal pathway

  • HU Ying-ying  HAN Yan-yan  ZHAO Jia-wei  YANG Ling  LIU Wen  ZUO Ji*
Author information +
History +

Abstract

Objective By constructing mortalin stably expressing ovarian cancer cell lines in A2780 and A2780/cis, we demonstrate the role of mortalin in the ovarian cancer cell growth. Methods CCK-8 assay was used to measure cell viability in the overexpression mortalin group compared with the control group. The flow cytometry analysis was used to understand the effect of upregulated mortalin on the ovarian cancer cell cycle. Western blotting was used to determine the expression and phosphorylation level of MAPK/ERK and JNK/SAPK signal pathways. Results The results showed that increased expression of mortalin could accelerate ovarian cancer cell proliferation and promote G1 transition, leading to a faster restoration of normal distribution of cell cycle. We found that mortalin overexpression significantly activated p-Raf and p-ERK1/2, but not p-JNK. Conclusion The results demonstrate that mortalin effect on the ovarian cancer cell proliferation contributes to active the MAPK-ERK signaling pathway.

Key words

Mortalin / Ovarian cancer / Cell cycle / MAPK-ERK signaling pathway / Plasmid construction / CCK-8 / Western blotting / Human

Cite this article

Download Citations
HU Ying-ying HAN Yan-yan ZHAO Jia-wei YANG Ling LIU Wen ZUO Ji*. Mortalin promotes ovarian cancer cell growth through MAPK-ERK signal pathway[J]. Acta Anatomica Sinica. 2014, 45(3): 338-343 https://doi.org/10.3969/j.issn.0529-1356.2014.03.008

References

[1]Singh AP, Senapati S, Ponnusamy M P. Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer[J]. Lancet Oncol, 2008, 9(11): 1076-1085.
[2]Auersperg N, Maines-Bandiera SL, Dyck HG. Ovarian carcinogen-esis and the biology of ovarian surface epithelium[J]. J Cell Physi-ol, 1997, 173(2): 261-265.
[3]Farley J, Ozbun LL,  Birrer MJ. Genomic analysis of epithelial ovarian cancer[J]. Cell Res, 2008, 18(5): 538-548.
[4]Hishiya A, Takayama S. Molecular chaperones as regulators of cell death[J]. Oncogene, 2008, 27(50): 6489-6506.
[5]Kaul SC,  Deocaris CC,  Wadhwa R. Three faces of mortalin: a housekeeper, guardian and killer[J]. Exp Gerontol, 2007, 42(4):  263-274.
[6]Wadhwa R, Kaul SC, Ikawa Y. Identification of a novel member of mouse hsp70 family. Its association with cellular mortal phenotype[J]. J Biol Chem, 1993, 268(9): 6615-6621.
[7]Yang L, Zhao MX, Liu W, et al. Effect of Grp75 on the alteration of apoptosis related gene Bax and NF-KB induced by glucose deprivation[J]. Acta Anatomic Sinica, 2009,40(4):594-598.(in Chinese)
杨玲, 赵明霞, 刘雯, 等. 葡萄糖调节蛋白75对缺糖诱导的凋亡相关基因Bax和NF-KB改变的影响[J]. 解剖学报,2009,40(4):594-598.
[8]Pizzatti L, Sa LA, de Souza JM. Altered protein profile in chronic myeloid leukemia chronic phase identified by a comparative proteomic study[J]. Biochim Biophys Acta, 2006, 1764(5): 929-942.
[9]Rozenberg P, Kocsis J, Saar M. Elevated levels of mitochondrial mortalin and cytosolic HSP70 in blood as risk factors in patients with colorectal cancer[J]. Int J Cancer, 2013, 133(2): 514-518.
[10]Takano S, Wadhwa R, Yoshii Y. Elevated levels of mortalin expression in human brain tumors[J].Exp Cell Res, 1997, 237(1): 38-45.
[11]Wadhwa R, Takano S, Kaur K. Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis[J]. Int J Cancer, 2006, 118(12): p. 2973-2980.
[12]Yi X, Luk JM, Lee NP. Association of mortalin (HSPA9) with liver cancer metastasis and prediction for early tumor recurrence[J]. Mol Cell Proteomics, 2008, 7(2): 315-325.
[13]Yang L, Li H, Jiang Y. Inhibition of mortalin expression reverses cisplatin resistance and attenuates growth of ovarian cancer cells[J]. Cancer Lett, 2013, 336(1): 213-221.
[14]Zhou BB,  Elledge SJ, The DNA damage response: putting checkpoints in perspective[J]. Nature, 2000, 408(6811):  433-439.
[15]Beere HM, Wolf BB, Cain K. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome[J]. Nat Cell Biol, 2000, 2(8): 469-475.
[16]Yang L, Guo W, Zhang Q. Crosstalk between Raf/MEK/ERK and PI3K/Akt in suppression of Bax conformational change by Grp75 under glucose deprivation conditions[J]. J Mol Biol, 2011, 414(5): 654-666.
[17]Boulton TG, Nye SH, Robbins D J. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF[J]. Cell, 1991, 65(4): 663-675.
[18]Kyosseva SV. Mitogen-activated protein kinase signaling[J]. Int Rev Neurobiol, 2004, 59: 201-220.
[19]Shaul YD, Seger R. The MEK/ERK cascade: from signaling specificity to diverse functions[J]. Biochim Biophys Acta, 2007, 1773(8):  1213-1226.
[20]Marshall CJ. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase[J]. Curr Opin Genet Dev, 1994, 4(1): 82-89.
[21]Steelman LS, Pohnert SC. Shelton JG. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis[J]. Leukemia, 2004, 18(2): 189-218.

Funding

the National Natural Science Foundation of China

Accesses

Citation

Detail

Sections
Recommended

/