PMID- 21667021
OWN - NLM
STAT- MEDLINE
DCOM- 20120111
LR  - 20110704
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 39
IP  - 3
DP  - 2011 Sep
TI  - Early in vitro passages of breast cancer cells are differentially susceptible to 
      retinoids and differentially express RARbeta isoforms.
PG  - 577-83
LID - 10.3892/ijo.2011.1070 [doi]
AB  - The effect of retinoids on breast cancer has been predominantly studied in vitro, 
      on established cell lines, which in biology differ significantly from primary 
      tumor cells. Little is known on whether early in vitro passages of breast cancer 
      cells (EPBCCs) are differentially sensitive to retinoids and differentially 
      express retinoid acid receptors (RARs) and retinoid X receptors (RXRs). We have 
      previously identified a novel RARbeta isoform (RARbeta5) and hypothesized that it may 
      serve as a potential target of retinoids in EPBCCs. Breast cancer cells isolated 
      from primary tumors were cultured in vitro for 6-12 passages (EPBCCs) and their 
      epithelial origin was confirmed by a cocktail of antibodies against cytokeratins. 
      EPBCCs were treated for 4 days with 1.0 microM of all-trans retinoic acid (atRA), 
      9-cis retinoic acid (9cRA) or 4-hydroxy-phenylretinamide (4-HPR) and their 
      viability determined by MTT assay. Among nine EPBCCs consistently grown in vitro, 
      three were resistant to the above retinoids, five were susceptible to atRA, four 
      to 4-HPR and two to 9cRA, suggesting that patients with breast carcinomas may 
      differentially respond to various retinoids. All EPBBCs differentially expressed 
      RARalpha, RARgamma, RXRalpha, RXRbeta proteins and RARbeta5 and RARbeta2 mRNAs. However, only one 
      EPBCC (BCA-2) expressed RARbeta5 at mRNA and protein level and it was resistant to 
      retinoids, both in vitro and in a xenograft tumor assay. RARbeta5 suppression by 
      siRNA in BCA-2 cells increased their susceptibility to atRA. No correlation was 
      found between sensitivity of EPBCCs to the above retinoids and RARbeta5 and RARbeta2 
      mRNA expression. atRA reduced RARbeta expression in most EPBCCs suggesting that this 
      retinoid receptor is most probably the prime target of retinoids in breast 
      cancer. These data may have clinical implication in selecting patients with 
      breast cancer that would benefit the most from clinical trials with retinoids.
FAU - Peng, Xinjian
AU  - Peng X
AD  - Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, 
      Chicago, IL 60616, USA.
FAU - Green, Albert
AU  - Green A
FAU - Shilkaitis, Anne
AU  - Shilkaitis A
FAU - Zhu, Yonghua
AU  - Zhu Y
FAU - Bratescu, Laura
AU  - Bratescu L
FAU - Christov, Konstantin
AU  - Christov K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110607
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - 0 (retinoic acid receptor beta)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*drug therapy/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Protein Isoforms
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Retinoic Acid/*biosynthesis/genetics
MH  - Retinoids/*pharmacology
MH  - Xenograft Model Antitumor Assays
EDAT- 2011/06/15 06:00
MHDA- 2012/01/12 06:00
CRDT- 2011/06/14 06:00
PHST- 2011/02/25 00:00 [received]
PHST- 2011/04/18 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2012/01/12 06:00 [medline]
AID - 10.3892/ijo.2011.1070 [doi]
PST - ppublish
SO  - Int J Oncol. 2011 Sep;39(3):577-83. doi: 10.3892/ijo.2011.1070. Epub 2011 Jun 7.