Linkage of Methionine Dependence and Other Features of Malignancy

  • Robert M. HoffmanEmail author
  • Richard W. Erbe
Part of the Methods in Molecular Biology book series (MIMB, volume 1866)


Cancer cells have an elevated methionine (MET) requirement compared to normal cells and are termed MET dependent. Cancer cells were isolated in MET-restricted (MR) medium that reverted from MET dependence to MET independence. Increased MET biosynthesis was not a prerequisite for reversion to MET independence, indicating that MET dependence was not due to reduced endogenous MET synthesis. MET-independent revertants of cancer cells concomitantly reverted for some of the other properties associated with malignancy: Of the 13 MET-independent revertants isolated 5 showed increased anchorage dependence as reflected by reduced cloning efficiencies in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and 3 altered their cell morphology significantly. Eight of the 13 revertants have increased chromosome numbers. Thus, by selecting for MET independence, it is possible to obtain heterogeneous reduced-malignancy revertants, indicating further a relationship between altered MET metabolism and other fundamental properties of oncogenic transformation.

Key words

Methionine dependence Methionine synthase Cancer cells Revertants Methionine independence Chromosomes Anchorage dependence Serum dependence Cell morphology Transmethylation 


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.AntiCancer, Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of CaliforniaSan DiegoUSA
  3. 3.Pediatrics and MedicineUniversity at BuffaloBuffaloUSA
  4. 4.Division of GeneticsThe Women and Children’s Hospital of BuffaloBuffaloUSA

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