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 journalArticle

Abstract

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
Volume59
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

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Paxillin
Focal Adhesion Protein-Tyrosine Kinases
Tretinoin
Tyrosine
Phosphorylation
Estrogen Receptors
Breast Neoplasms
Retinoid X Receptors
Focal Adhesions
Retinoids
Cell Adhesion
Cell Line
Retinoic Acid Receptors
Fibronectins
Integrins
Complementary DNA
Western Blotting
Phosphates

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. / Zhu, Wei Yong; Jones, Carol S.; Amin, Sonal; Matsukuma, Karen; Haque, Moneera; Vuligonda, Vidyasagar; Chandraratna, Roshantha A S; De Luca, Luigi M.

In: Cancer Research, Vol. 59, No. 1, 01.01.1999, p. 85-90.

Research output: Contribution to journalArticle

Zhu, WY, Jones, CS, Amin, S, Matsukuma, K, Haque, M, Vuligonda, V, Chandraratna, RAS & De Luca, LM 1999, 'Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells', Cancer Research, vol. 59, no. 1, pp. 85-90.
Zhu WY, Jones CS, Amin S, Matsukuma K, Haque M, Vuligonda V et al. Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. Cancer Research. 1999 Jan 1;59(1):85-90.
Zhu, Wei Yong ; Jones, Carol S. ; Amin, Sonal ; Matsukuma, Karen ; Haque, Moneera ; Vuligonda, Vidyasagar ; Chandraratna, Roshantha A S ; De Luca, Luigi M. / Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. In: Cancer Research. 1999 ; Vol. 59, No. 1. pp. 85-90.
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abstract = "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.",
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