Pituitary adenylate cyclase-activating peptide/vasoactive intestinal peptide receptors in human normal mammary gland and breast cancer tissue

Jul 16, 2005Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology

Receptors for PACAP and VIP in Normal and Cancerous Human Breast Tissue

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Abstract

PACAP and VIP receptors are expressed in human breast tissue, with higher levels in cancerous tissue compared to normal tissue.

The three subclasses of PACAP/VIP receptors (VPAC1, VPAC2, and PAC1) were identified in both normal and malignant breast tissue.
mRNA analysis revealed various isoforms of PAC1 receptors due to alternative splicing.
Immunohistochemistry showed that these receptors are present in epithelial cells and leukocytes within carcinomatous tissue.
A weaker presence of PAC1 receptors was noted in normal tissue, while cancer tissue demonstrated a strong density of all receptor subclasses.
The functional activity of PAC1, VPAC1, and VPAC2 receptors was confirmed through their coupling to adenylate cyclase stimulation.
The findings suggest a potential role for PACAP and VIP in breast tumor progression, although further validation with more samples is needed.

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Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) bind similarly to VPAC1 and VPAC2 receptors, whereas PACAP binds with higher affinity than VIP to PAC1 receptors. Here we demonstrate by different approaches the expression of the three subclasses of PACAP/VIP receptors in human normal and malignant breast tissue. At the mRNA level, reverse transcription-polymerase chain reaction experiments showed VPAC1 and VPAC2 receptors as well as various isoforms (null, hip/hop) of PAC1 receptors due to alternative splicing. At the protein level, Western blot experiments revealed the three subclasses of receptor although no conclusive differences could be established when comparing control, peritumoral and tumoral tissue samples. Immunohistochemistry showed the distribution of these receptors: they were located at epithelial cells in normal and cancer conditions but also in leukocytes at the stromal level in carcinomatous tissue. A weaker immunostaining of PAC1 receptors in normal tissue and a strong density of the three PACAP/VIP receptor subclasses in cancer tissue may be related to differential expression patterns during breast tumor progression but more samples need to be studied to validate this hypothesis. PAC1, VPAC1 and VPAC2 receptors were functional, as shown by their coupling to adenylate cyclase stimulation: VIP, PACAP-27 and PACAP-38 behaved similarly at this level, whereas both VPAC receptors acted alike as shown by means of specific peptide agonists and antagonists. The present results together with the known presence of PACAP and VIP in the mammary gland support a paracrine/autocrine involvement of both peptides at this level in physiological and pathological conditions, i.e. during malignant transformation.

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Pituitary adenylate cyclase-activating peptide/vasoactive intestinal peptide receptors in human normal mammary gland and breast cancer tissue

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