Identification of a novel co-transcription of P450/1A1 with telomerase in A549.
A novel co-transcription of CYP1A1 with hTERT, the active subunit of telomerase has been identified in alveolar epithelial cancer cell line (A549). This correlation was confirmed by chemically inducing the transcription of CYP1A1 in four cell lines: control normal lung cells (CCD-32Lu); alveolar epithelial cancer cell line (A549); large cell carcinoma (H460) and drug resistance large cell carcinoma (COR-L23/5010) observing a concomitant increase in hTERT mRNA level. In addition, siRNA was used to silence CYP1A1 transcription in A549 observing a decrease in the level of hTERT mRNA. The transcription correlation between CYP1A1 and hTERT may suggest a possible new mechanism for cancer therapy based on alternative gene targets. The co-transcription showed that the AhR pathway plays an active role in the activation of CYP1A1 which subsequently activates hTERT transcription. This study showed that the expression of CYP1A1 and CYP1A2 are cell specific and CYP2E1 and GSTM1 may not play a significant role in lung carcinogenesis.
Shervington
A
A
University of Central Lancashire, Department of Biological Sciences, Preston, PR1 2HE, UK. aashervington@uclan.ac.uk
Mohammed
K
K
Patel
R
R
Lea
R
R
D002460:Cell Line; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019098:Telomerase; C509186:TERT protein, human