Insulin-regulated aminopeptidase/placental leucil Aminopeptidase (IRAP/P-lAP) and angiotensin IV-forming activities are modified in serum of rats with breast cancer induced by N-methyl-nitrosourea

Anticancer Res. 2006 Mar-Apr;26(2A):1011-4.

Abstract

Background: In previous reports, changes in oxytocinase activity in human breast cancer tissue and in the serum of N-methyl-nitrosourea (NMU)-induced rat mammary tumors were described. Insulin-regulated aminopeptidase (IRAP) has been identified with oxytocinase and has also been referred to as placental leucine aminopeptidase (P-LAP).

Materials and methods: The IRAP/P-LAP activity in rat serum was assayed to analyze the putative role that IRAP/P-LAP may play in regulating mammary gland carcinogenesis induced by NMU. Furthermore, as it has been recently described that IRAP/P-LAP is the angiotensin IV (Ang IV) receptor AT4, the activities of Ang IV-forming aminopeptidase N (APN) and aminopeptidase B (APB) were also assayed.

Results: Changes in serum IRAP/P-LAP and Ang IV-forming APB activities were found in rats with mammary tumors induced by NMU. Both activities were greatly increased, although the Ang IV-forming APN activity was not modified.

Conclusion: These changes in aminopeptidase activities may reflect the local functional status of their substrates, which can be selectively activated or inhibited in the affected tissue as a result of specific conditions brought about by the tumor. Thus, these enzymatic activities may be involved in the promotion and progression of breast cancer through oxytocin (OT), vasopressin (AVP) and/or renin-angiotensin system (RAS) misregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / blood*
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / biosynthesis
  • Angiotensin II / blood
  • Animals
  • Cystinyl Aminopeptidase / blood*
  • Female
  • Mammary Neoplasms, Experimental / blood
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / enzymology*
  • Methylnitrosourea
  • Rats
  • Rats, Wistar
  • Receptors, Angiotensin / blood

Substances

  • AT4 receptor
  • Receptors, Angiotensin
  • Angiotensin II
  • angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-
  • Methylnitrosourea
  • Aminopeptidases
  • Cystinyl Aminopeptidase
  • leucyl-cystinyl aminopeptidase
  • aminopeptidase B