The role of histamine in human mammary carcinogenesis: H3 and H4 receptors as potential therapeutic targets for breast cancer treatment.

Abstract

There is increasing evidence that describes a histamine role in normal and cancer cell proliferation. To better understand the importance of histamine in breast cancer development, the expression of histamine H3 (H3R) and H4 (H4R) receptors and their association with proliferating cell nuclear antigen (PCNA), histidine decarboxylase (HDC) and histamine content were explored in mammary biopsies. Additionally, we investigated whether H3R and

Histamine in cancer: The dual faces of the coin

“…9 Similarly, in the human pancreatic carcinoma PANC-1 cells, histamine at low concentration (0.01 μM) increases tumor cell proliferation whereas at high concentration (10 μM) decreases cell proliferation via receptor activation thereby inducing a G 0 /G 1 cell cycle arrest associated with partial stimulation of cell differentiation. 10 The results reported by Medina et al 11 in their article published in this issue of Cancer Biology & Therapy, well illustrate this bivalent behaviour of histamine in regulating tumor cell growth. The authors investigate, for the first time, the expression of the H 3 and H 4 receptors in human benign and malignant mammary lesions.…”

Histamine Receptors as Potential Therapeutic Targets for Cancer Drug Development

“…Recent data indicate that H 3 R and H 4 R are expressed in human biopsies of benign lesions and breast carcinomas being the level of their expression significantly higher in carcinomas, confirming that H 3 R and H 4 R are present not only in cell lines but also in the human breast tissue. Furthermore, the expression of H 3 R is highly correlated with proliferation and histamine production in malignant lesions while the 50% of malignant lesions expressed H 4 R, all of them corresponding to metastases or high invasive tumours (Medina et al, 2008). The identification of histamine receptor subtypes and the elucidation of their role in the development and growth of human mammary carcinomas may represent an essential clue for advances in breast cancer treatment.…”

“…This outcome was associated to an induction of apoptosis determined by Annexin-V staining and TdT-mediated UTP-biotin Nick End labelling (TUNEL) assay, which was blocked by the specific H 4 R antagonist JNJ7777120. Also H 4 R agonists exerted a 2.5-fold increase in the cell senescence while reduced migration (Medina et al, 2008(Medina et al, , 2010c(Medina et al, , 2011b. Furthermore, histamine differentially regulates expression and activity of matrix metalloproteinases, cell migration and invasiveness through H 2 R and H 4 R in MDA-MB-231 cells modulating H 2 O 2 intracellular levels (Cricco et al, 2011).…”

Adrenoceptors and Breast Cancer: Review Article

“…Studies the age-related immunohistochemical (IHC) expression of ER, HER-2 in 2,227 tumors using age as a continuous variable (21) . Estrogen receptors (ERs) are overexpressed in human breast cancers (BCs) and associated with differentiated tumors and with a more favorable prognosis (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) . Paradoxically, ERs mediate the mitogenic action of estrogens in human BC cells and the efficacy of antiestrogens in adjuvant therapy of primary tumors.…”