Assessing methylation of ATG5 and LC3 related to Autophagy in patients with breast cancer

Mojtaba Mohammadnejad pahmadani, Raheleh Safaejavan, Shohre Zare Karizi


Background: Breast Cancer is one of the leading causes of cancer deaths among women worldwide. The role of epigenetics as a distinct mechanism to alter gene expression in a tissue-specific manner has emerged as an important mechanism in the pathophysiology of cancer. One of the most important of epigenetic factor is DNA methylation which has been studied in various cancers.

Method: The methylation specific high resolution melting (MS-HRM) method was used for promoter methylation status investigation of ATG5 and LC3 genes in 30 breast tumor samples and 30 adjacent normal samples.

Results: For the ATG5 and LC3 genes, were methylated 2 (6.67%) of tumor samples and 1 (3.34%) of tumor samples out of max 30 tumor samples, respectively. Also, the rest of the samples showed no methylation change in their promoter region, and statistical results demonstrated that there is no significant difference between the promoter methylation status of these genes in tumor samples and normal samples (P>0.05).


Breast Cancer, DNA Methylation, MS-HRM Method, Autophagy, ATG5, LC3

Full Text:



Ahmadi, A. M., Ghasemi, H., Nooshin, S., Zayani, Z., Karizi, S. Z., & Karimipoor, M. (2018). Assessing Gene Expression and Methylation of KMT2D and IGF2 Genes in Patients with Non-Small Cell Lung Cancer. Cancer and Clinical Oncology, 7(1), 55.

Cho, D.-H., Jo, Y. K., Kim, S. C., Park, I. J., & Kim, J. C. (2012). Down-regulated expression of ATG5 in colorectal cancer. Anticancer research, 32(9), 4091-4096.

Christensen, B. C., Kelsey, K. T., Zheng, S., Houseman, E. A., Marsit, C. J., Wrensch, M. R., . . . Kushi, L. H. (2010). Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. PLoS genetics, 6(7), e1001043.

Coleman, M. P. (1999). Opinion: why the variation in breast cancer survival in Europe? Breast Cancer Research, 1(1), 22.

Dent, R., Trudeau, M., Pritchard, K. I., Hanna, W. M., Kahn, H. K., Sawka, C. A., . . . Narod, S. A. (2007). Triple-negative breast cancer: clinical features and patterns of recurrence. Clinical Cancer Research, 13(15), 4429-4434.

Eccles, S. A., Aboagye, E. O., Ali, S., Anderson, A. S., Armes, J., Berditchevski, F., . . . Bryant, H. E. (2013). Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research, 15(5), R92.

Eskelinen, E.-L., & Saftig, P. (2009). Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1793(4), 664-673.

Ferlay, J., Shin, H. R., Bray, F., Forman, D., Mathers, C., & Parkin, D. M. (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127(12), 2893-2917.

Howell, A., Anderson, A. S., Clarke, R. B., Duffy, S. W., Evans, D. G., Garcia-Closas, M., . . . Harvie, M. N. (2014). Risk determination and prevention of breast cancer. Breast Cancer Research, 16(5), 446.

Jiang, Z.-F., Shao, L.-J., Wang, W.-M., Yan, X.-B., & Liu, R.-Y. (2012). Decreased expression of Beclin-1 and LC3 in human lung cancer. Molecular biology reports, 39(1), 259-267.

Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., . . . Yoshimori, T. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO journal, 19(21), 5720-5728.

Karantza, V., & White, E. (2007). Role of autophagy in breast cancer. Autophagy, 3(6), 610-613.

Kim, M. S., Song, S. Y., Lee, J. Y., Yoo, N. J., & Lee, S. H. (2011). Expressional and mutational analyses of ATG5 gene in prostate cancers. Apmis, 119(11), 802-807.

Kisen, G. Ø., Tessitore, L., Costelli, P., Gordon, P. B., Schwarze, P. E., Baccino, F. M., & Seglen, P. O. (1993). Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells. Carcinogenesis, 14(12), 2501-2505.

Micheli, A., Baili, P., Quinn, M., Mugno, E., Capocaccia, R., & Grosclaude, P. (2003). Life expectancy and cancer survival in the EUROCARE-3 cancer registry areas. Annals of Oncology, 14(suppl_5), v28-v40.

Nooshin, S., Karizi, S. Z., Karimipoor, M., & Nooshin, M. (2018). The Methylation Analysis of KLF11 and PCDH9 Genes in Patients with Non-Small Cell Lung Cancer. Cancer and Clinical Oncology, 7(1), 47.

Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014). Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer research.

Rouzier, R., Perou, C. M., Symmans, W. F., Ibrahim, N., Cristofanilli, M., Anderson, K., . . . Wagner, P. (2005). Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clinical Cancer Research, 11(16), 5678-5685.

Shen, Y., Li, D.-D., Wang, L.-L., Deng, R., & Zhu, X.-F. (2008). Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy, 4(8), 1067-1068.

Tanida, I., Ueno, T., & Kominami, E. (2004). LC3 conjugation system in mammalian autophagy. The international journal of biochemistry & cell biology, 36(12), 2503-2518.

Widschwendter, M., Siegmund, K. D., Müller, H. M., Fiegl, H., Marth, C., Müller-Holzner, E., . . . Laird, P. W. (2004). Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer research, 64(11), 3807-3813.

Yoshioka, A., Miyata, H., Doki, Y., Yamasaki, M., Sohma, I., Gotoh, K., ... & Monden, M. (2008). LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers. International journal of oncology, 33(3), 461-468.



  • There are currently no refbacks.

Copyright (c) 2019 Arash sajad

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.