The renin angiotensin system in endometrial cancer — ASN Events
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  3. The renin angiotensin system in endometrial cancer

The renin angiotensin system in endometrial cancer (#134)

Riazuddin Mohammed 1 2 , Sarah Delforce 1 2 , Yu Wang 1 2 , Rodney Scott 1 3 4 , Nicole M Verrills 1 5 , Kirsty G Pringle 1 2 , Eugenie R Lumbers 1 2
  1. School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia
  2. Pregnancy and Reproduction Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  3. Information Based Medicine Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  4. Division of Molecular Medicine, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales, Australia
  5. Cancer Research Program, University of Newcastle, Newcastle, New South Wales, Australia

Endometrial cancer is the most common gynecological malignancy. Its incidence is rising, due to the prevalence of obesity and hyperoestrogenism.

Tissue renin angiotensin system (RAS) are known to stimulate angiogenesis, cell proliferation and migration, all of which can potentiate cancer growth and spread. This primarily occurs via angiotensin (Ang) II acting on the angiotensin type 1 receptor (AT1R). The rate-limiting enzyme in the renin angiotenisn cascade is renin, which is produced soley by the kidneys. Therefore the (pro)renin receptor ((P)RR), which allows activation of the renin precursor, prorenin, and local production of Ang II, is very important in tissue RAS. The prorenin/(P)RR interaction also stimualtes intracellular signaling directly, via Wnt and mitogen activated protein kinases (MAPK) signaling pathways, which are implicated in cancer growth and spread. Prorenin and the (P)RR however, have not been investigated in any cancer type to date.

Out study characterised the RAS pathways within primary human endometrial cancer tissue and invitro models of endometrial cancer. We found that endometrioid endometrial cacners (n=30, grades 1-3) express both prorenin and (P)RR mRNA and have significantly greater levels of these proteins than normal adjacant endometrial tissue. Additionally, endometrial cancer tissue had greater expression of components of the proliferative pro-angiogenic Ang II-AT1R pathway.

Similarly, we found in 2 endometrial epithelial cancer cell lines (ECC-1 and RL95-2), very high expression of (P)RR as well as expression of prorenin mRNA. The expression of other RAS genes differed between the two cell lines however; ECC-1 had higher expression of angiotensin converting enzyme (ACE) mRNA, whereas RL95-2 cells had higher ACE2 and an absence of angiotensinogen (AGT) mRNA.

This suggests that the prorenin/(pro)renin receptor interaction may be functionally important to endometrial cancer growth and development, and importantly raises the exciting possibly of the repositioning existing anti-hypertensive drugs that target renin, towards cancer treatment.