Premium
Are The Intrarenal Hormones The Culprit in Renal Cell Carcinoma?
Author(s) -
Jackson Cynthia Ann,
Canionero Dee Dee
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1087.18
Subject(s) - losartan , angiotensin ii , endocrinology , renal cell carcinoma , medicine , renin–angiotensin system , cancer research , kidney , cell growth , carcinogenesis , angiotensin receptor , receptor , cancer , biology , blood pressure , biochemistry
Renal Cell Carcinoma (RCC) is a form of kidney cancer that originates in the lining of the renal tubules. Over a decade ago, long‐term use of angiotensin converting enzyme inhibitor to treat hypertension was associated with a decreased incidence of various types of cancer in hypertensive patients. Subsequently, recent studies have demonstrated that angiotensin II, via activation of the angiotensin II type 1 receptor (AT1R), stimulates cellular proliferation and migration and thus may play a role in the pathophysiology of cancer. The present study was designed to evaluate the role of the renin angiotensin system (RAS) in RCC. BrdU proliferation assays were utilized to examine the effects of the various intrarenal components of the RAS in human renal carcinoma cells, ACHN. In addition, immunocytochemistry studies were used to detect the specific signal transduction pathway involved in tumorigenesis. ACHN cells treated with captopril decreased the proliferation rate by 90%. Blockade of angiotensin II receptor subtype 1 (AT1R, losartan‐treated) and subtype 2 (AT2R, PD123319‐treated) significantly decreased proliferation rate by 15% and 85%, respectively. cAMP activity was reduced in the PD123319‐treated cells and augmented in the losartan‐treated cells. The results of these studies demonstrate that angiotensin II via the AT2R rather than the AT1R regulates cellular proliferation in ACHN renal carcinoma cells during tumorigenesis, possibly through the cAMP pathway. These studies will enhance our ability to develop new therapy and/or treatments specifically directed at various biomarkers to reduce the morbidity associated with renal cell carcinoma.