The RIα subunit of protein kinase A controls serum dependency and entry into cell cycle of human mammary epithelial cells

Giampaolo Tortora, Stefano Pepe, Caterina Bianco, Gustavo Baldassarre, Alfredo Budillon, Timothy Clair, Yoon Sang Cho-Chung, A. Raffaele Bianco, Fortunato Ciardiello

Research output: Contribution to journalArticlepeer-review

Abstract

MCF-10A, a nontransformed mammary epithelial cell line, requires a mixture of hormones and growth factors for optimal cell proliferation. In this report ne show that when MCF-10A cells are cultured in serum free medium they become quiescent and accumulate in G0/G1 phases of the cell cycle. Following addition of complete medium to quiescent cells, MCF-10A cells enter into the S phase within 15-18h and resume the cell cycle distribution of proliferating cells within 24 h. Measurement of RIα subunit of the cAMP-dependent protein kinase (PKA) shows a 10- to 15-fold increase in protein levels at 6h following complete medium addition, thus preceding cell entry into the S phase. Retroviral vector-mediated overexpression of RIα, but not of RIIβ or Cα subunits of PKA, enables MCF-10A cells to grow in serum-free medium. In addition, RIα downregulation by specific antisense oligodeoxynucleotide treatment or following infection with a retroviral vector containing the RIα cDNA in antisense orientation determines growth arrest of proliferating MCF-10A cells and is able to partially block S phase entry of quiescent MCF-10A cells following complete medium addition. These results suggest that RIα/PKAI is involved in the control of cell cycle progression of mammary epithelial cells at a G1 to S transition border, and that its overexpression is able to overcome serum and growth factors requirement for cell proliferation.

Original languageEnglish
Pages (from-to)3233-3240
Number of pages8
JournalOncogene
Volume9
Issue number11
Publication statusPublished - Nov 1994

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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