Detection of VIP receptors in MNU-Induced breast cancer in rats: Implications for breast cancer targeting

Vasoactive intestinal peptide (VIP) is a 28 amino acid neuropeptide with a wide range of biological activities. Receptors for VIP (VIP-R) are overexpr essed in breast cancer, where they may have diagnostic and therapeutic impl ications. Although N-methyl nitrosourea (MNU)-induced breast cancer in rats is used extensively as a model to study mammary carcinogenesis, there is n o information about the expression of VIP-R in this model. Therefore, the p urpose of this study was to investigate the presence of VIP-R in MNU-induce d breast cancer in rats so that this model can be used to perform studies i nvolving VIP-R. Breast cancer was induced in 36-day-old virgin female Sprag ue-Dawley rats, by a single intravenous injection of MNU (50 mg/kg body wei ght). The breast tumors were detected 100-150 days after injection. The nor mal and cancerous rat breast tissue were excised and 20 mu sections were in cubated with 40 nM fluorescein-labeled VIP (Fluo-VIP(TM)), in the presence and absence of 1000-fold excess unlabeled VIP, pituitary adenylate cyclase activating polypeptide (PACAP) or secretin. The sections were visualized un der a fluorescence microscope and photographed. Fluo-VIP(TM) stained rat br east cancer tissue homogeneously and to a much greater extent than normal r at breast tissue (p < 0.05). This staining was specific as indicated by dis placement of Fluo-VIP(TM) by excess unlabeled VIP and PACAP. Displacement o f Fluo-VIP(TM) by secretin indicated the probable presence of VIP receptors of type VPAC1 (VIP receptor subtype1) in the rat breast. These data sugges t that, as in human breast cancer, VIP-R, predominantly of type VPAC1, are overexpressed in MNU-induced rat breast cancer tissue as compared to the no rmal rat breast tissue. Thus, MNU-induced rat breast cancer model can be us ed as a tool to study the functional role of VIP-R in human mammary carcino genesis and VIP-R mediated active breast cancer targeting. This could have implications in the diagnosis, prognosis and therapy of human breast cancer .