Expressions and Clinical Significance of Autophagy-related Genes ATG2B, ATG4D, ATG9B in Breast Carcinoma

ZHANG Xue-mei, LI Hong-jiang, WANG Da. et al

Abstract

To investigate the expressions and clinical significance of autophagy-related gene 2B （ATG2B），autophagy-related gene 4D （ATG4D） , autophagy-related gene 9B（ATG9B） in breast cancer cell lines and breast cancer. Methods Cancer Browser screening was applied to study the differential expressions ofATG2B, ATG4D, ATG9Bgenes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues. The relationships between the expressions of these genes and clinicopathological characteristics were further analyzed. Results Cancer Browser screening found abnormal expressions of ATG2B, ATG4D, ATG9Bin breast cancer （ P=0.015， P=0.028， P=0.040）. All four breast cancer cell lines expressed ATG2B, ATG4D, ATG9B,and the expression of ATG2B, ATG9B was significantly lower than positive control ( P<0.001), but ATG4D expression was higher than positive control ( P<0.001). The expressions of ATG2B, ATG4D, ATG9B in breast cancer were all lower than those in the adjacent normal tissues ( P<0.001, P=0.031, P<0.001). Furthermore, the expression of ATG2B was correlated with ER ( r =0.949， P=0.015), and the expression of ATG4D was related to age ( r =-0.449， P=0.005), the expression of ATG9B was correlated to lymph node metastasis and cytokeratin 5/6 status ( r =0.339， P=0.043; r =0.533， P=0.043). Conclusion ATG2B, ATG4D, ATG9Bgenes shows low expressions in breast cancer, which may become new molecular markers for the prognosis of breast cancer.

 

Keywords: Autophagy-related genes, Breast carcinoma, Expression 

 

Full Text:

PDF


References


Chen W. Zheng R, Zeng H .et al. Annual report on status of cancer in China, 2011. Chin J Cancer Res,2015 ;27(1);2-12.

Stanley RE, Ragusa MJ , Hurley JH. The beginning of the end; how scaffolds nucleate autophagosome biogenesis. Trends Cell Biol,2014 ;24( 1): 73-81.

Qin Z, Xue J , He Y,elal. Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population. Gene,2013;527(2);491 -495.

Scott RC, Juhasz G, Neufeld TP. Direct induction of autophagy by Atgl inhibits cell growth and induces apoptotic cell death. Curr Biol,2007; 17( 1) : 1-11.

Thedieck K. Holzwarth B, Prentzell MT,et al. Inhibition of mTORCl by astrin and stress granules prevents apoptosis in cancer cells. Cell,2013; 154(4) :859-874.

Kang MR, Kim MS, Oh JE, et al. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol ,2009;217(5); 702-706.

Kyostila K, Syrja P, Jagannathan V, et al. A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease. PLoS Genet, 2015; 11(4):el005169. doi:10. 1371/journal, pgen. 1005169.

Zavodszky E, Vicinanza M, Rubinsztein DC. Biology and trafficking of ATG9 and ATG16L1, two proteins that regulate autophagosome formation. FEBS Lett, 2013; 587 ( 13 ); 1988- 1996.


Refbacks

  • There are currently no refbacks.