Pilar Carrera María, Ramírez-Expósito María Jesús, Dueñas Basilio, Dolores Mayas María, Jesús García María, De la Chica Susana, Cortés Pedro, Ruíz-Sanjuan María, Martínez-Martos José Manuel
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
Anticancer Res. 2006 Mar-Apr;26(2A):1011-4.
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).
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.
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.
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.
在先前的报告中，描述了人类乳腺癌组织以及N-甲基亚硝基脲（NMU）诱导的大鼠乳腺肿瘤血清中催产素酶活性的变化。胰岛素调节氨肽酶（IRAP）已被确定为催产素酶，也被称为胎盘亮氨酸氨肽酶（P-LAP）。
检测大鼠血清中的IRAP/P-LAP活性，以分析IRAP/P-LAP在调节NMU诱导的乳腺致癌作用中可能发挥的假定作用。此外，由于最近有报道称IRAP/P-LAP是血管紧张素IV（Ang IV）受体AT4，因此还检测了生成Ang IV的氨肽酶N（APN）和氨肽酶B（APB）的活性。
在NMU诱导的乳腺肿瘤大鼠中发现血清IRAP/P-LAP和生成Ang IV的APB活性发生变化。两种活性均大幅增加，而生成Ang IV的APN活性未改变。
这些氨肽酶活性的变化可能反映了其底物的局部功能状态，由于肿瘤引起的特定条件，底物在受影响组织中可被选择性激活或抑制。因此，这些酶活性可能通过催产素（OT）、血管加压素（AVP）和/或肾素-血管紧张素系统（RAS）失调参与乳腺癌的发生和发展。
