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 overexpressed in breast cancer, where they may have diagnostic and therapeutic implications. Although N-methyl nitrosourea (MNU)-induced breast cancer in rats is used extensively as a model to study mammary carcinogenesis, there is no information about the expression of VIP-R in this model. Therefore, the purpose of this study was to investigate the presence of VIP-R in MNU-induced breast cancer in rats so that this model can be used to perform studies involving VIP-R. Breast cancer was induced in 36-day-old virgin female Sprague-Dawley rats, by a single intravenous injection of MNU (50 mg/kg body weight). The breast tumors were detected 100-150 days after injection. The normal and cancerous rat breast tissue were excised and 20 micro sections were incubated 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 under a fluorescence microscope and photographed. Fluo-VIP(TM) stained rat breast cancer tissue homogeneously and to a much greater extent than normal rat breast tissue (p < 0.05). This staining was specific as indicated by displacement of Fluo-VIP(TM) by excess unlabeled VIP and PACAP. Displacement of Fluo-VIP(TM) by secretin indicated the probable presence of VIP receptors of type VPAC1 (VIP receptor subtype 1) in the rat breast. These data suggest 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 normal rat breast tissue. Thus, MNU-induced rat breast cancer model can be used as a tool to study the functional role of VIP-R in human mammary carcinogenesis and VIP-R mediated active breast cancer targeting. This could have implications in the diagnosis, prognosis and therapy of human breast cancer.
Dagar
S
S
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, 60612-7231, USA.
Sekosan
M
M
Rubinstein
I
I
Onyüksel
H
H
D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D019793:Fluorescein; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology*; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis / Q000096:biosynthesis*
D000477:Alkylating Agents; D018005:Receptors, Vasoactive Intestinal Peptide; D008770:Methylnitrosourea; D019793:Fluorescein