Abstract
Abstract
Background: Activins belong to the family of transforming growth factor-β and the mature proteins (activin-A, -B and AB) are formed by the dimerization of two β-subunits (βA & βB). The biological activities of activins are tightly regulated by their binding protein, follistatin. Activin-A is the most studied isoform in the biology of colorectal cancer (CRC) and none of the earlier studies explored the expression profiles of the other activins as well as follistatin.
Objectives: This study measured the gene and protein expressions of activin βA- and βB-subunits together with follistatin in paired malignant and remote non-cancerous specimens that were obtained at the different stages of malignancy from patients diagnosed with primary sporadic CRC.
Materials and methods: Archived paired cancerous and non-cancerous colonic specimens were obtained from a total of 30 patients diagnosed with primary CRC. Following the identification of cancer stages by expert histopathologists, the genes and proteins of the targeted molecules were measured by quantitative RT-PCR and immunohistochemistry, respectively.
Results: The genes and proteins of both activin βA- and βB-subunits alongside follistatin were comparable between the non-cancerous specimens obtained at the different stages of cancer. Nevertheless, significant up-regulations in the genes and proteins of βA-subunit and follistatin simultaneously with a marked inhibition of the βB-subunit were detected in the malignant specimens compared with their counterpart non-malignant tissues. Additionally, the βA-subunit and follistatin showed substantial increases in the malignant sites as cancer progressed and the highest levels were detected in stage IV compared with the earlier stages.
Opposingly, the βB-subunit decreased gradually and significantly with cancer advancement and the protein expression was completely lost at stage IV.
Conclusions: This study suggests that the overexpression of activin βA-subunit and follistatin may contribute to colon carcinogenesis and tumor progression, whereas the βB-subunit could be associated with anti-tumorigenic activities. However, more studies are still needed to measure the levels of the activin mature proteins (e.g. activin-A, -B and -AB) together with follistatin to precisely characterize their roles in CRC tumorigenesis.
Acknowledgment: This project was funded by the DEANSHIP OF SCIENTIFIC RESEARCH AT UMM AL-QURA UNIVERSITY; Project (17-MED-1-01-0068).
Citation Format: Mohammed Abbas Baghdadi, Jawwad Ahmad, Shakir Idris, Jamal Zekri, Abdelrazak Meliti, Hosam Alardati, Aiman Alsaegh, Mohammed Aslam, Bassem Refaat. The expression profiles of activins and follistatin at the different stages of colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3680.