A proposal for the physiological significance of mdr1 and Bcrp1/Abcg2 gene expression in normal tissue regeneration and after cancer therapy.
Cellular multi-drug resistance (MDR), which often develops in cancer cells of patients subjected to anti-cancer treatment, remains a significant barrier to successful cancer therapy. One of the principal causes of cellular MDR development is an increased expression of ABC-transporter genes such as mdr1 and Bcrp1/Abcg2. Despite many years of intensive research, the natural biological role of mdr1 in the context of cancer has remained elusive. Some hints about this role came, however, from an observation that P-gp, the mdr1 encoded protein, is expressed widely in stem cells and from the discovery that P-gp possesses an anti-apoptotic activity independently of exogenous drug application. Here, we discuss our own and other groups' recently published works and propose an integrated view of mdr1 and Bcrp1/Abcg2 activity during tissue regeneration in normal tissues as part of a stress-induced regeneration genetic program and in cancerous tissues in response to cancer therapy.
Israeli
David
D
Genethon Centre National de la Recherche Scientifique UMR 8115, 1 bis rue de l'Internationale, 91002 Evry cedex, France. israeli@genethon.fr
Ziaei
Simin
S
Gonin
Patrick
P
Garcia
Luis
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D015870:Gene Expression; D019450:Genes, MDR / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins