Elsevier

The Journal of Nutrition

Volume 131, Issue 11, November 2001, Pages 3047S-3050S
The Journal of Nutrition

Specific Amino Acid Deficiency Alters the Expression of Genes in Human Melanoma and Other Tumor Cell Lines1,2

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This study determined the effect of tyrosine (Tyr) and phenylalanine (Phe) deprivation on protein expression and phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4)/stress-activated protein/Erk kinase (SEK1), a metastasis suppressor gene. Differential display and suppressive subtractive hybridization techniques identified genes modulated by Tyr and Phe deprivation. Expression of MKK4/SEK1 protein varied widely among human A375, A375SM and SB2 melanoma, PC-3 and DU145 prostate cancer, and MDA-MB-231 breast cancer cell lines and within the different lines. Phosphorylation of the MKK4/SEK1 protein similarly varied. No differences in MKK4/SEK1 gene expression or in the 41 other metastasis and tumor suppressor genes were found in A375 melanoma cells cultured in Tyr- and Phe-deprived media. A number of up-regulated and down-regulated genes in A375 melanoma cells were identified by differential display and suppressive subtractive hybridization that were pertinent to regulation of cytoskeletal organization, cell movement, gene transcription and metastasis. Two tumor marker genes, the gene for enolase and FUS/CHOP, were down-regulated by Tyr and Phe deprivation. This study shows that tumor cells display heterogeneity in their response to deprivation of Tyr and Phe and that these amino acids may be signaling molecules that regulate gene expression and function in tumor cells.

Key words:

neoplasm
amino acid
gene expression

Abbreviations used:

MEM
minimum essential medium
MKK4
mitogen-activated protein kinase kinase 4
PCR
polymerase chain reaction
RACE
rapid amplification of the cDNA ends
SEK1
stress-activated protein/Erk kinase

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1

Presented as part of the 11th Annual Research Conference on Diet, Nutrition and Cancer held in Washington, DC, July 16–17, 2001. This conference was sponsored by the American Institute for Cancer Research and was supported by the California Dried Plum Board, The Campbell Soup Company, General Mills, Lipton, Mead Johnson Nutritionals, Roche Vitamins Inc. and Vitasoy USA. Guest editors for this symposium publication were Ritva R. Butrum and Helen A. Norman, American Institute for Cancer Research, Washington, DC.

2

Supported by grants 01A022 from the American Institute for Cancer Research and CA77604 from the National Cancer Institute.