Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells

Wei Yong Zhu, Carol S. Jones, Sonal Amin, Karen Matsukuma, Moneera Haque, Vidyasagar Vuligonda, Roshantha A.S. Chandraratna, Luigi M. De Luca

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Treatment of estrogen receptor (ER)-positive MCF-7 human breast cancer cells with retinoic acid (RA) inhibited cell growth and increased cell adhesion to fibronectin. In contrast, ER- MDA-MB-231 cells failed to respond. Western blot analysis showed that tyrosine phosphorylation of two major bands at M(r) 125,000 and M(r) 68,000 was induced by RA in ER+ MCF-7 human breast carcinoma cells. However, this induction was a late phenomenon detectable at 12 and 24 h, but not within 3 h. A similar increase of tyrosine phosphorylation by RA was observed in ER+ human breast cancer cell lines T- 47D and ZR-75-1, but not in the ER- cell lines MDA-MB-231, MDA-MB-453, and MDA-MB-468. Focal adhesion kinase and paxillin, which localize in focal adhesion plaques and may play important roles in the integrin signaling pathway, were identified as the major proteins showing RA-induced tyrosine phosphorylation. The retinoid X receptor-selective compound SR11237 failed to induce tyrosine phosphorylation, indicating that retinoid X receptor activation is not involved in this phenomenon. In contrast, stable overexpression of a truncated RA receptor (RAR) α cDNA, RARα403, with strong RAR dominant negative activity prevented the increase in tyrosine phosphate, suggesting that RAR signaling is involved in RA-induced tyrosine phosphorylation. Tyrosine phosphorylation was induced the most by the RAR-α (193836), followed by RAR-γ (194433), but was not significantly induced by RAR-β (193174)-selective retinoids. This study demonstrates a coordinated albeit relatively late effect of RA on cell adhesion and tyrosine phosphorylation in ER+ human breast cancer cells and suggests RAR-α as the major responsible retinoid receptor.

Original languageEnglish (US)
Pages (from-to)85-90
Number of pages6
JournalCancer Research
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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