Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Mice and in a Chemically-Induced Model of Colon Cancer.

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the family by quantitative real-time PCR. Two animal models of colon cancer were used: mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of and are reduced in human colon cancer tissues compared to those of normal tissues. deletion suppresses the tumor development and growth in mice, while deficiency exacerbates the tumorigenicity. deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in mice; however, deficiency does not change these expressions. In the AOM/DSS model, deficiency worsens the tumorigenesis. In conclusion, deficiency confers tumor-suppressing effects in mice, but deficiency worsens the tumorigenicity in both and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.