Gene expression signature of parathion-transformed human breast epithelial cells.

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Calaf GM, Roy D

Gene expression signature of parathion-transformed human breast epithelial cells.

Int J Mol Med. 2007 May;19(5):741-50.

PubMed ID

17390078 [ View in PubMed

]

Abstract

Environmental substances seem to be involved in the etiology of breast cancers. Many studies have found an association between human cancer and exposure to agricultural pesticides such as the organophosphorous pesticides. Parathion is a cholinesterase inhibitor that induces the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. The primary target of action in insects is the nervous system whereby pesticides inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Atropine is a parasympatholytic alkaloid used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to determine the effect of parathion and atropine on cell transformation of human breast epithelial cells in vitro. These studies showed that parathion alone was able to induce malignant transformation of an immortalized human breast epithelial cell line, MCF-10F as indicated by increased cell proliferation, anchorage independency and invasive capabilities. There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the parathion-treated cells. However, atropine significantly inhibited this increase. In a human cell cycle array of 96 genes, 13 of them were altered by parathion treatment. Among the genes affected were the cyclins, such as cyclin D3, the cyclin-dependent kinases (CDKs) such as CDK41 and the minichromosome maintenance deficient (MCM) MCM2 and MCM3. It is suggested that parathion influences human breast epithelial cell transformation and is an initiator factor in the transformation process in breast cancer.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Choline	Cholinesterase	Protein	Humans	Unknown	Product of	Details
Choline salicylate	Cholinesterase	Protein	Humans	Unknown	Product of	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Atropine	Approved Vet Approved	CCNA1	8900	upregulated	Atropine results in increased expression of CCNA1 mRNA	13q13.3
Atropine	Approved Vet Approved	CCNE1	898	upregulated	Atropine results in increased expression of CCNE1 mRNA	19q12
Atropine	Approved Vet Approved	CCNE2	9134	upregulated	Atropine results in increased expression of CCNE2 mRNA	8q22.1
Atropine	Approved Vet Approved	CDC20	991	upregulated	Atropine results in increased expression of CDC20 mRNA	1p34.2
Atropine	Approved Vet Approved	CDK1	983	upregulated	Atropine results in increased expression of CDK1 mRNA	10q21.2
Atropine	Approved Vet Approved	MCM4	4173	upregulated	Atropine results in increased expression of MCM4 mRNA	8q11.21
Atropine	Approved Vet Approved	MCM6	4175	upregulated	Atropine results in increased expression of MCM6 mRNA	2q21.3