ABC gene expression profiles have clinical importance and possibly form a new hallmark of cancer

Abstract

Adenosine triphosphate-binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate-binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate-binding cassette gene expression profiles (signatures), based on the expression of all 49 human adenosine triphosphate-binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate-binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate-binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients-breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real-time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate-binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate-binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 (official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers. Graphical abstract699800T UB0010.1177/1010428317699800Tumor BiologyDvorak et al. research-article2017Research Article 2 Tumor Biology

The effects of growth hormone on therapy resistance in cancer

“…The ABC-transporter family has 48 members, classified into seven groups ABC-A through ABC-G based on sequence similarities, and involved in efflux of xenobiotics as well as biological macromolecules like peptides and lipids from the cytoplasmic compartment of the mammalian cell [134][135][136] . Excellent reviews have delved into the mechanism of action, subtypes, molecular functions, substrate specificities, and role in health and disease of ABC-transporters, especially in cancer [134,[137][138][139][140][141][142] . Over the last 30 years, numerous studies have established ABC-transporters as a major determinant of failure of antineoplastic chemotherapy.…”

Downregulation of ABC Transporters in Non-neoplastic Tissues Confers Better Prognosis for Pancreatic and Colorectal Cancer Patients

“…Chloride channels, encoded by the ABCC7 (official symbol CFTR ) gene, are a family of anion-selective channels involved in the regulation of the excitability of neurons, skeletal, cardiac and smooth muscle, cell volume regulation, transepithelial salt transport and the acidification of intra- and extracellular compartments. Surprisingly, an important role of CFTR protein in gastrointestinal cancer development was suggested by several recent works 24 , 25 and also by our previous results 11 . The ABCC8 protein functions as a modulator of ATP-sensitive potassium channels and insulin release, and together with ABCD2 was recently suggested to play a putative role in breast cancer progression and prognosis of patients 14 , 26 .…”

“…Several significant connections between individual ABC genes and clinicopathological features were revealed. We recently proposed the existence of ABC gene expression profiles common to more types of tumors based on a comprehensive bioinformatic analysis of our results concerning ABC gene expression profiles in different tumor tissues together with a literature review 11 .…”

“…Several research groups showed the importance of ABC gene expression profiles in tumor tissues and their relationships to clinicopathological features. ABC expression profiles in tumor tissues were the main theme of our previous article, where the summary of the relevant literature was presented and the existence of general ABC profiles in tumors was demonstrated 11 .…”

Cancer stem cells, stemness markers and selected drug targeting: metastatic colorectal cancer and cyclooxygenase-2/prostaglandin E2 connection to WNT as a model system

“…Therefore, ABCG2 has applications not only in the identification of the CSCs, but also for allowing the possibility of blocking its function as one way for improving selective drug targeting of tumors and their CSC population during the course of anticancer chemotherapy [41] . Despite the supportive evidence that ABCG2 is a stem cell marker, there are limitations since the exact role of the ABCG2 signalling pathway and its regulation is not well understood [42,43] . Although the molecular mechanisms regulating ABCG2 expression are not clearly understood, it is likely that the MYC oncogene plays an important role in promoting its expression in some cancers [44] .…”