Genes amplified and overexpressed in human multidrug-resistant cell lines.

摘要: Multidrug resistance (MDR) is associated with overproduction of Mr 170,000 membrane proteins (P-glycoproteins) caused by either gene amplification, transcriptional activation, or both. In rodents the amplified domain comprises genes that encode P-glycoproteins and at least five unrelated genes, one which encodes calcium-binding protein sorcin. The amplification increased expression these always includes P-glycoprotein-encoding (pgp1 in hamsters, homologous to mdr1 humans). human MDR cells only elevated has been shown thusfar, although another P-glycoprotein encoding (mdr3, hamster pgp3) closely linked. Here we show homolog sorcin resides on chromosome 7 like genes. Furthermore, classes designated 4, 5, 6 are coamplified mdr3 ovarian carcinoma cell line 2780AD, strongly suggests overall structure same as rodents. Class was moderately highly overexpressed this line. Four other lines also have much higher overexpression than expected from relatively low levels (2- 30-fold) amplification. This contrasts results previous work rodent cells, increase mRNA usually parallels copy number. Although four mdr3, its undetectable. Our confirm central role (pgp1) suggest different cross-resistance patterns not due differential