Quantitative correlation of homogeneously stained regions on chromosome 10 with dihydrofolate reductase enzyme in human cells.

Abstract:

:Gene amplification may be visualized within a chromosome as a homogeneously stained region (HSR) and HSRs have rarely been reported in human tumor cells with identification of the amplified gene. A parental line and seven clones derived from KB cells resistant to methotrexate (MTX) contain dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; EC 1.5.1.3), ranging from 0.007 unit/mg in the parent to 0.369 unit/mg in clone 7A with a 13,000-fold increase in resistance to MTX. The enzyme is identical to DHFR from other human sources, including that from leukemic patients. A HSR localized to the long arm of chromosome 10(q26) is present in clones selected at or above 2.5 microM MTX. Increase in number of 10q per cell, increase in number of HSR, and increasing amounts of DHFR correlate well. The chromosome change is stable with time as is enzyme production even in the absence of selection by MTX. No clone has shown double minutes. The gene copy number is low. The stability and low gene copy in the presence of large HSRs differ from the pattern described for murine tumors. A human gene for DHFR may be associated with the long arm of chromosome 10.

authors

Wolman SR,Craven ML,Grill SP,Domin BA,Cheng YC

doi

10.1073/pnas.80.3.807

subject

Has Abstract

pub_date

1983-02-01 00:00:00

pages

807-9

issue

3

eissn

0027-8424

issn

1091-6490

journal_volume

80

pub_type

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