Correlation between Ubiquitin E3 Ligases (SIAHs) and Heat Shock Protein 90 in Breast Cancer Patients

Sabour Takanlou L., Çeçener G., Sabour Takanlou M., Öztürk Nazlıoğlu H., Tezcan Ünlü H., Işık Ö., ...More

IRANIAN JOURNAL OF PUBLIC HEALTH, vol.51, pp.1836-1846, 2022 (Peer-Reviewed Journal)

  • Publication Type: Article / Article
  • Volume: 51
  • Publication Date: 2022
  • Doi Number: 10.18502/ijph.v51i8.10270
  • Journal Indexes: Science Citation Index Expanded, Social Sciences Citation Index, Scopus, CAB Abstracts, CINAHL, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.1836-1846


Background: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR,

and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among

breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a

considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling

pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the

most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to

specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS

signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.

Methods: The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85

invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018–

2019, and its association with the clinicopathologic variables of patients was evaluated.

Results: HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor

tissue of patients with breast cancer. Moreover, this study observed a significant association between the high

expression of SIAH2/ HSP90 with ER status, high expression of HSP90 with Recurrence/ Metastasis, and

high expression of SIAH2 with Ki-67 proliferation index.

Conclusion: The HSP90 and SIAH2 expressions play a significant role in breast cancer development by

combining the experimental and clinical data obtained from the literature.