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.
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).


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.


CONCLUSIONS
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.
Pilar Carrera
María
M
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
Ramírez-Expósito
María Jesús
MJ
Dueñas
Basilio
B
Dolores Mayas
María
M
Jesús García
María
M
De la Chica
Susana
S
Cortés
Pedro
P
Ruíz-Sanjuan
María
M
Martínez-Martos
José Manuel
JM
D000626:Aminopeptidases / Q000097:blood*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D010122:Cystinyl Aminopeptidase / Q000097:blood*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D008770:Methylnitrosourea; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000097:blood
C090830:AT4 receptor; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D008770:Methylnitrosourea; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; C019721:aminopeptidase B