Overexpression of wild-type p53 overrides the mitogenic effect of RIα subunit of protein kinase A in human breast cells

V. Damiano, F. Ciardiello, C. Bianco, G. Baldassarre, G. Di Isernia, S. Pepe, A. Ruggiero, G. Merlo, A. R. Bianco, G. Tortora

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Abstract

Protein kinase A type I (PKAI) and its regulatory subunit RIα are overexpressed in cancer cells and are induced by mitogenic hormones and growth factors in non-transformed cells. RIα/PKAI are directly involved in the G1>S transition and cell proliferation of non-transformed human breast MCF-10A cells. Retroviral vector-mediated overexpression of RIα in these cells (MCF-10A RIα) confers the ability to grow in serum-free medium. p53 controls a G1 check point before transition to the S phase, playing a key role in the regulation of cell proliferation and in the preservation of DNA integrity. In this study we evaluated the interaction of p53 and RIα on cell cycle progression and cell proliferation of MCF-10A cells. Retroviral vector-mediated overexpression of wild-type p53 in the MCF-10A neo and MCF-10A RIα cells determined a marked inhibition of RIα protein expression in MCF-10A-p53 cells and induced G0/G1 accumulation, cell growth arrest and changes in cell morphology not due to apoptosis in both MCF-10A-p53 and MCF-10A RIα-p53 cells. On the other hand, in the MCF-10A RIα cells we observed an increased expression of the endogenous p53, although these cells were still able to proliferate. These results suggest that overexpression of wild-type p53 acts in a dominant fashion to abrogate the RIα induction of G1>S transition and cell proliferation. Moreover, overexpression of RIα leads to increased synthesis of endogenous p53 which, however, is unable to interfere with the Rice-dependent mitogenic signalling.

Original languageEnglish
Pages (from-to)331-336
Number of pages6
JournalInternational Journal of Oncology
Volume7
Issue number2
Publication statusPublished - 1995

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Keywords

  • Cell cycle
  • Cell proliferation
  • p53
  • Protein kinase A

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Damiano, V., Ciardiello, F., Bianco, C., Baldassarre, G., Di Isernia, G., Pepe, S., Ruggiero, A., Merlo, G., Bianco, A. R., & Tortora, G. (1995). Overexpression of wild-type p53 overrides the mitogenic effect of RIα subunit of protein kinase A in human breast cells. International Journal of Oncology, 7(2), 331-336.