P14ARF is down-regulated during tumour progression and predicts the clinical outcome in human breast cancer

Anticancer Res. 2013 May;33(5):2185-9.

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.

Keywords: breast cancer; cell cycle; cell senescence; p14; p16; qPCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / secondary
  • Breast / metabolism*
  • Breast / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / secondary
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Medullary / mortality
  • Carcinoma, Medullary / secondary
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Copy Number Variations
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Neoplasm Grading
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Telomerase / genetics
  • Telomerase / metabolism
  • Tumor Suppressor Protein p14ARF / genetics*
  • Tumor Suppressor Protein p14ARF / metabolism

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p14ARF
  • TERT protein, human
  • Telomerase