Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells.
Epidemiological studies indicate that there is a positive correlation between alcohol consumption and the risk of breast cancer. Experimental results demonstrate that ethanol is a tumor promoter and chronic ethanol exposure enhances metastasis and growth of breast cancer. The present study used an in vitro model to investigate the molecular mechanism(s) underlying tumor promoting effects of ethanol. With differential display reverse transcription polymerase chain reaction, we demonstrated that human ribosomal large subunit protein L7a (rpL7a) was an ethanol-responsive factor in T47D breast cancer cells. The results of northern blot hybridization revealed that the effect of ethanol on L7a expression was duration- and concentration-dependent. Initial exposure resulted in a 2-fold increase in rpL7a level, whereas a longer exposure period produced a down-regulation. Ethanol had little effect on the stability of rpL7a mRNA; however, the transcription rate of rpL7a was significantly increased by ethanol. Ethanol-induced up-regulation of rpL7a was not a simple stress response, because other stress inducers, such as heat shock, did not affect the expression of rpL7a. Furthermore, breast cancer cells expressed higher level of rpL7a than normal mammary epithelial cells. Ribosomal proteins are known to play an important role in translational regulation, and they have been implicated in the control of cellular transformation, tumor growth, aggressiveness and metastasis. Specially, rpL7a activates the trk oncogene by contributing an amino-terminal-activating sequence to the receptor kinase domain of trk. Thus, ethanol-induced alteration of rpL7a expression may mediate the promoting effects of ethanol on breast cancer development.
Zhu
Y
Y
Department of Anatomy, West Virginia University School of Medicine, Morgantown 26506-9128, USA.
Lin
H
H
Li
Z
Z
Wang
M
M
Luo
J
J
D000428:Alcohol Drinking / Q000009:adverse effects*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015513:Oncogene Proteins; D016133:Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012307:Risk Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002492:Central Nervous System Depressants; D018076:DNA, Complementary; D015513:Oncogene Proteins; C057838:RPL7A protein, human; D012269:Ribosomal Proteins; C065400:oncogene protein trk; D000431:Ethanol