P14ARF Is Down-regulated During Tumour Progression and Predicts the Clinical Outcome in Human Breast Cancer

  1. KEFAH MOKBEL1,2
  1. 1The London Breast Institute, Princess Grace Hospital, London, U.K.
  2. 2Department of Breast Surgery, St. George's Hospital and Medical School, University of London, London, U.K.
  3. 3Metastasis and Angiogenesis Research Group, Department of Surgery, School of Medicine, Cardiff University, Cardiff, Wales, U.K.
  4. 4The Brunel Institute of Cancer Genetics and Pharmacogenomics, Brunel University, London, U.K.
  1. Correspondence to: Professor Kefah Mokbel, London Breast Institute, the Princess Grace Hospital, 45 Nottingham Place, London W1U 5NY, U.K. E-mail: kefahmokbel{at}hotmail.com

Abstract

The objective of this study was to determine the mRNA expression for p14 and p16 in a cohort of women with breast cancer. Materials and Methods: Breast cancer specimens (N= 127) and normal tissue (N=23) specimens were studied. Transcript levels were determined using quantitative polymerase chain reaction (PCR), and were correlated with clinicopathological data collected over 10 years. Results: Higher p14 mRNA transcript levels were associated with non-cancerous background tissue specimens (median copy numbers: 103 vs. 4, p=0.0095), with better overall and disease-free survival, and in TNM2 stage tumours (TNM2 vs. TNM1, 27.2 vs. 3.5, p=0.049; TNM1/TNM2 vs. TNM3/4, 26 vs. 2, p=0.009). There was no significant relationship between p16 levels and clinicopathological parameters. A correlation between p14 and human telomerase reverse transcriptase (hTERT) levels was observed (r=0.406, p=0.00005). Conclusion: p14 expression seems to increase initially in early breast cancer and decrease with further tumour progression. p14 may be induced to counteract immortalisation and hTERT surge.

  • Received January 16, 2013.
  • Revision received April 8, 2013.
  • Accepted April 9, 2013.
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