Loss of anti-proliferative effect of all-trans retinoic acid in advanced stage of breast carcinogenesis

Hyun Ahn Eun, Chia Cheng Chang, David A. Talmage

Research output: Contribution to journalArticlepeer-review


Background: Mechanisms by which the inhibitory effect of retinoic acid on tumor growth is attenuated as tumors progress to more advanced stages are unclear. Materials and Methods: This study utilizes a novel cell culture system of human breast epithelial cells (HBEC). Immortal (M13SV1), weakly tumorigenic (M13SV1-R2), and highly tumorigenic (M13SV1-R2N1) transformed Type I HBEC were derived sequentially from the same parental Type I HBEC (stem cells) developed from reduction mammoplasty of healthy women. Effects of all-trans retinoic acid (AT-RA) on the growth, protein expression of RAR-α, β and γ, and RARE transcriptional activation were determined. Results and Conclusion: AT-RA reduces proliferation rates of immortal and weakly tumorigenic cells, but not highly tumorigenic cells. This loss of response of highly tumorigenic cells to AT-RA is associated with overexpression of p185c-erbB2/neu. It is not associated with decreased RAR-α, β or γ expression, or activation by AT-RA; RAR-α, β and γ are expressed and AT-RA increases RARE transcriptional activity in all cell lines tested in this study.

Original languageEnglish (US)
Pages (from-to)2899-2904
Number of pages6
JournalAnticancer research
Issue number8
StatePublished - Aug 2009
Externally publishedYes


  • All-trans retinoic acid
  • Breast cancer
  • Proliferation
  • Tyrosine phosphorylation
  • c-erbB2/neu

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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