Effects of 3-methylcholanthrene on the transcriptional activity and mRNA accumulation of the oncogene hWAPL.
hWAPL is a human oncogene associated with uterine cervical cancer. Here, we demonstrate that hWAPL transcription is induced by 3-methylcholanthrene (3-MC) in the cervical carcinoma-derived cell line SiHa. hWAPL transcription was analyzed with evaluation of the mRNA and heterogeneous nuclear RNA (hnRNA) levels by quantitative real time PCR analysis. Flow cytometric analysis suggested that the alteration of hWAPL mRNA levels is independent of cell cycle profile. We also found that DMSO and some components of FBS affect hWAPL transcription. Interestingly, when the aryl hydrocarbon receptor (AhR) function was inhibited by alpha-naphthoflavone (ANF), the induction of hWAPL transcription by 3-MC was greater than that in AhR-functioning normal cells. These observations suggest that there are complex mechanisms regulating the transcription of hWAPL. Furthermore, mRNA level of a mouse homolog of hWAPL in mouse uterus was induced by 3-MC injection into the abdominal cavity. Thus, some effects from 3-MC exposure on uterus may be mediated by the unscheduled overexpression of hWAPL.
Kuroda
Masahiko
M
Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. kuroda@tokyo-med.ac.jp
Oikawa
Kosuke
K
Yoshida
Keiichi
K
Takeuchi
Aya
A
Takeuchi
Masaru
M
Usui
Masahiko
M
Umezawa
Akihiro
A
Mukai
Kiyoshi
K
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes / Q000187:drug effects*; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D014599:Uterus / Q000187:drug effects; D000097722:Cohesins
D002352:Carrier Proteins; D008748:Methylcholanthrene; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C488092:WAPL protein, human; D000097722:Cohesins; C496335:WAPL protein, mouse