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

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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.

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

  • Oncology
  • Cancer Research

Cite this

Zhu, W. Y., Jones, C. S., Amin, S., Matsukuma, K., Haque, M., Vuligonda, V., ... De Luca, L. M. (1999). Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. Cancer Research, 59(1), 85-90.

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, 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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