Expression of mRNA coding for TGF-beta and its receptors in irradiated human breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin.
OBJECTIVE
The effect of X-irradiation on the expression of mRNAs coding for transforming growth factor beta (TGF-beta) and its receptors was compared in human breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin.


METHODS
Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the estimation of mRNAs expression for TGF-beta1, TGF-beta2 and TGF-beta type I and II receptors in the unirradiated and irradiated cells of two sublines of MCF-7 cells--sensitive (MCF-7(wt)) and resistant (MCF-7(DOX/R)) to doxorubicin.


RESULTS
X-irradiation caused an increase in TGF-beta1 coding for mRNA expression in both breast cancer cell lines tested and an elevation of TGF-beta2 mRNA expression in doxorubicin-resistant subline. The down-regulation of TGF-beta type I and II receptors in the irradiated MCF-7(DOX/R) cells was revealed at the transcriptional level.


CONCLUSIONS
The results of our study show that the development of refractoriness of used tumor cells to anti-cancer drug doxorubicin, at least partly, can be caused by the impairment in TGF-beta signaling pathway.
Institute of Cell Biology, NAS of Ukraine, Lviv 79005, Ukraine.
Inna
I
Chorna
Oleksandr
O
Fedorenko
Leonid
L
Datsyuk
Rostyslav
R
Stoika
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014965:X-Rays
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004317:Doxorubicin; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II