Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines

David T. Grabowski, Russell O. Pieper, Bernie W. Futscher, Walter A. Deutsch, Leonard C. Erickson, Mark Kelley

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We initiated this study to determine whether three structurally related bifunctional alkylating agents could induce the expression of a presumptive human DNA repair gene. The gene chosen for this study is known to encode the ribosomal phosphoprotein PO, but ironically may also share functions related to DNA repair. We now show by Northern analysis that PO is induced by L-phenylalanine mustard, 4-hydroperoxycyclophosphamide and mechlorethamine, which are DNA-damaging agents commonly used as chemotherapeutic antitumor agents. In further support of its involvement in DNA repair is the finding of a 30- to 50-fold constitutive overexpression of the PO gene in human tumor cell lines that are Mer-, cells which lack O6-methylguanine methyltransferase activity, when compared to Mer+ cell lines. This constitutively elevated level of PO in Mer- cell lines, which are thus DNA repair defective for O6-alkyguanine lesions, was not observed for other genes tested, including the human ribosomal gene S17 whose mRNA steady-state levels were uniformly the same in both Mer- and Mer+ cells. Taking these data together, it appears that increased levels of PO are somehow linked to DNA repair, and increased expression of PO may compensate for the decreased O6-methylguanine DNA methyltransferase activity in Mer- cells. Furthermore, the PO gene has also been shown to be overexpressed in colorectal tumors and polyps and the sera of some systemic lupus erythematosus patients contain antibodies against PO. The titer of the anti-PO antibodies rises significantly during lupus psychosis.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalCarcinogenesis
Volume13
Issue number2
StatePublished - Feb 1992
Externally publishedYes

Fingerprint

Phosphoproteins
Tumor Cell Line
Antineoplastic Agents
Tumors
Tumor
DNA
DNA Repair
Repair
Cells
Gene
Genes
Line
Cell
perfosfamide
Methyltransferases
Antibody
Antibodies
Cell Line
Mechlorethamine
Melphalan

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Grabowski, D. T., Pieper, R. O., Futscher, B. W., Deutsch, W. A., Erickson, L. C., & Kelley, M. (1992). Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. Carcinogenesis, 13(2), 259-263.

Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. / Grabowski, David T.; Pieper, Russell O.; Futscher, Bernie W.; Deutsch, Walter A.; Erickson, Leonard C.; Kelley, Mark.

In: Carcinogenesis, Vol. 13, No. 2, 02.1992, p. 259-263.

Research output: Contribution to journalArticle

Grabowski, DT, Pieper, RO, Futscher, BW, Deutsch, WA, Erickson, LC & Kelley, M 1992, 'Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines', Carcinogenesis, vol. 13, no. 2, pp. 259-263.
Grabowski, David T. ; Pieper, Russell O. ; Futscher, Bernie W. ; Deutsch, Walter A. ; Erickson, Leonard C. ; Kelley, Mark. / Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. In: Carcinogenesis. 1992 ; Vol. 13, No. 2. pp. 259-263.
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