Both HIF-1_ and GAB1 can regulate Pim-1 in the papillary thyroid carcinoma

Date 21 October 2018
Event ESMO 2018 Congress
Session Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Topics Thyroid Cancer
Cancer Biology
Presenter Xin Zhu
Citation Annals of Oncology (2018) 29 (suppl_8): viii645-viii648. 10.1093/annonc/mdy302
Authors X. Zhu1, Q. Wen2, M. Ge2
  • 1Zhejiang Cancer Institution, Zhejiang Cancer Hospital, 310022 - Hangzhou/CN
  • 2Head And Neck Surgery, Zhejiang Cancer Hospital, 310022 - Hangzhou/CN

Abstract

Background

As a oncogene, Pim-1 has been proved to play key role in proliferation, apoptosis and angiogenesis. Thyroid cancer represents the most common malignancy in the endocrine system, and a marked increase in the incidence has occurred in recent years. Among them, papillary thyroid carcinoma (PTC) is the most common form. So it is worthwhile to discuss the function of Pim-1 in the development and progression of PTC.

Methods

34 PTC patients were selected to investigate the levels of Pim-1, HIF-1α and GAB1 protein by IHC. After hypoxia treatment for 24h, Westernblot was carried out to detect the Pim-1, HIF-1α and GAB1 in the PTC cell BCPAP and TPC-1. BCPAB was trasfected with GAB1 shRNA and Full-length vector to achieve GAB1 knockdown and overexpression. CCK-8 assay was used to measure the ell proliferation. The migration and invasion capacity were tested by wound-healing and transwell methods respectively.

Results

Both Pim-1 and HIF-1α were overexpressed in the PTC tissues and Pim-1 levels were significant correlated with HIF-1α. Meanwhile, Pim-1 had a significant relationship with the tumor number - patients with multiple tumor have a higher Pim-1 level than that have solitary tumor and HIF-1α showed a significant correlation with patients’ age. After bioinformatics screen, we found that there were 4 hypoxia response elements (HRE) in the Pim-1 promoter area, which suggested HIF-1α could transcriptional regulate Pim-1 directly. Moreover, hypoxia could signifcantly drive HIF-1α and Pim-1 elevation in both BCPAP and TPC-1. GAB1 was found to express higher in PTC tissues than that in the adjacent normal tissues and GAB1 level was significant associated with the tumor size. Morover, Pim-1 expression was significantly decrease and increase after GBA1 knockdown and overexpression in BCPAP. Meanwhile, GAB1 did not affect the cell viability but exerted a strong effect on the migration and invasion capacity of BCPAP. However, there was no change in GAB1 expression after hypoxia treatment in both BCPAP and TPC-1.

Conclusions

Taken together, our current data showed the important role of Pim-1 in the PTC. It also can be deduced that both HIF-1α and GAB1 are involved in the upstream regulation of Pim-1, but the detailed mechanism are different, which depended on the different tumor microenvironment.

Clinical trial identification

Legal entity responsible for the study

Zhejiang Cancer Hospital.

Funding

National Natural Science Foundation of China.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.