title: An alternative pathway for expression of p56lck from type I promoter transcripts in colon carcinoma.
abstract: The lymphoid-specific protein tyrosine kinase, p56lck which is essential for both T cell development and function, is aberrantly expressed in colon and small lung carcinoma lines. In this paper, we demonstrate p56lck is also expressed in colon tumour biopsies due predominantly or exclusively to the use of the lck type I promoter. In T leukaemia lines, the lck type I promoter requires binding sites for both Ets- and Myb-related transcription factors. In contrast, in colon tumour lines the activation of the lck type I promoter requires the Ets but not the Myb binding site. In these lines, a consensus binding site for HMG-related transcription factors, AACAAAG, is required for efficient lck type I promoter activity. Sox-4 is a candidate transcription factor for binding and activating the lck type l promoter in colon carcinoma cells. Co-expression of Ets-1 and Sox-4, but neither protein alone, was sufficient to activate the lck type l promoter in HeLa cells which do not normally express lck transcripts. These results suggest that aberrant expression of p56lck from the lck type l promoter in colon carcinoma arises from transcriptional activation mediated by Ets- and HMG-related transcription factors.
authors.affiliation: The AMGEN Research Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: McCracken
authors.forename: C S
authors.initials: CS
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Minden
authors.forename: N G
authors.initials: NG
authors.lastname: Miyamoto
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004357:Drug Synergism; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009378:Neoplasms, Multiple Primary / Q000201:enzymology / Q000235:genetics; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D012045:Regulatory Sequences, Nucleic Acid; D055751:SOXC Transcription Factors; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; D006609:High Mobility Group Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)