Alterations in RDINK4/ARF‐mediated en bloc regulation of the INK4‐ARF locus in human squamous cell carcinoma of the head and neck. Issue 7 (2nd December 2013)

• Record Type: Journal Article
• Authors: Poi, Ming J.; Knobloch, Thomas J.; Sears, Marta T.; Warner, Blake M.; Uhrig, Lana K.; Weghorst, Christopher M.; Li, Junan
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 7(2015:Jul.)
• Page Start: 532
• Page End: 542
• Publication Date: 2013-12-02
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22119
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mc22119-sec-0001" sec-type="section"> <p>The presence of <italic>RD</italic><sup><italic>INK4</italic>/<italic>ARF</italic></sup> (<italic>RD</italic>) enhancer in the <italic>INK4‐ARF</italic> locus provides a novel mechanism to simultaneously increase the transcription of <italic>p15</italic><sup><italic>INK4b</italic></sup> (<italic>p15</italic>), <italic>p14ARF</italic> (<italic>p14</italic>), and <italic>p16</italic><sup><italic>INK4a</italic></sup> (<italic>p16</italic>). While such upregulation can be repressed through interactions between <italic>RD</italic> and oncoproteins CDC6 and BMI1, little is known about the involvement of <italic>RD</italic> in cancer. In this study we investigated <italic>RD</italic> deletions in 30 squamous cell carcinoma of the head and neck (SCCHN) and the patient‐matched High At‐Risk Mucosa specimens (HARM, "phenotypically normal" tissues neighboring SCCHN foci but beyond the surgical resection margin). <italic>RD</italic> was deleted (homozygously/heterozygously) in SCCHN and HARM at the incidence of 36.7% (11/30) and 13.3% (4/30), respectively. In comparison, no <italic>RD</italic> deletion was detected in 26 oral buccal brush biopsy specimens from healthy donors. Both <italic>p16</italic> and <italic>p14</italic> were lowly expressed in SCCHN and HARM, and their mRNA expression levels were positively associated with each other (<italic>P</italic> < 0.01). Moreover, <italic>BMI1</italic> was highly expressed in both SCCHN and HARM, and <italic>BMI1</italic> overexpression was associated with <italic>p16</italic> downregulation in SCCHN (<italic>P</italic> < 0.05). These results indicate that <italic>RD</italic> deletion and <italic>BMI1</italic> overexpression frequently occur in the early stage of oral carcinogenesis and <italic>BMI1</italic> overexpression may downregulate the transcription of <italic>p16</italic> and <italic>p14</italic> through interfering with <italic>RD</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>