Sensitivity of human tumor cells to retinoids or combined treatment with retinoids and ionizing radiation is not dependent on RAR-beta 2 induction.
OBJECTIVE
The nuclear retinoic acid receptor beta 2 (RAR-beta2) is supposed to be a prognostic marker of retinoid sensitivity in patients after retinoid treatment. Therefore, we investigated the role of RAR-beta2 induction with respect to clonogenic survival of different human tumor cells under retinoid treatment alone or in combination with irradiation.


METHODS
The retinoid responsiveness of seven human tumor cell lines (HTB35, HTB43, SCC4, SCC9, MDA-MB231, HCT116, and CaSki) as well as one normal human skin fibroblast (HSF6) as control cells was analyzed by colony formation assay under retinoid and retinoid/radiation treatment. Basic mRNA levels of all retinoic acid receptors as well as the treatment-dependent modulation of mRNA and protein levels of RAR-beta were analyzed by RT-PCR and Western blot analysis under the different treatment conditions.


RESULTS
It could be shown that the clonogenic inactivation of tumor cells under retinoid treatment alone or in combination with irradiation was not correlated with the induction of RAR-beta on mRNA and protein level, respectively. The control cells (HSF6), however, demonstrated an induction.


CONCLUSIONS
The responsiveness of human tumor cells to retinoid treatment alone and particularly to combined treatment with irradiation is not necessarily associated with an induction of RAR-beta2 as it has been postulated so far. Thus, loss of RAR-beta induction in tumors does not seem to be a good prognostic factor for successful retinoid/radiation therapy, since RAR-beta-deficient tumors may also present strong retinoid responsiveness.
Blaese
Marcel A
MA
Section of Radiobiology and Molecular Environmental Research, Eberhards Karls University, Tübingen, Germany.
Santo-Hoeltje
Lan
L
Rodemann
H Peter
HP
D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006258:Head and Neck Neoplasms; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics*; D012176:Retinoids / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082925:retinoic acid receptor beta