Tumor Biology

, Volume 33, Issue 2, pp 307–314

AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer

SI: Epigenetics in Cancer

DOI: 10.1007/s13277-011-0266-2

Cite this article as:
Yu, Y., Yin, D., Hoque, M.O. et al. Tumor Biol. (2012) 33: 307. doi:10.1007/s13277-011-0266-2

Abstract

The purpose of this study is to determine the epigenetic changes and function of High in Normal-1 (HIN-1) in non-small cell lung cancer (NSCLC). HIN-1 expression was examined by semiquantitative RT-PCR before and after 5-aza-2′-deoxycytidine (5-aza) treatment in NSCLC cell lines. Promoter methylation status of HIN-1 was tested by methylation-specific PCR (MSP). Effect of forced expression of HIN-1 on different key molecules of AKT signaling pathway was tested by Western Blot analysis in H157 and H23 cell lines. Promoter methylations are inversely correlated with expression of HIN-1 in eight (H23, H157, 95D, H1299, H358, H1752, H460, A549) of ten NSCLC cell lines and re-expression was observed by 5-aza treatment. We then tested promoter methylation of HIN-1 in primary NSCLC tissues. Methylation was detected in 73 out of 152 (48%) NSCLC cases. Forced expression of HIN-1in NSCLC cell lines inhibited colony formation and induce apoptosis. Furthermore, overexpression of HIN-1 reduces the expression of phosphorated-AKT (p-AKT), c-myc, Bcl-2 and cyclinD1 while Bax was increased. Our data suggest that HIN-1 is a potential tumor suppressor gene in NSCLC, silenced by promoter hypermethylation and negatively regulate AKT signaling pathway.

Keywords

High in normal-1 methylationNon-small cell lung cancerAKT signaling pathwayApoptosis

Abbreviations

HIN-1

High in normal-1

NSCLC

Non-small cell lung cancer

MSP

Methylation specific

RT-PCR

Reverse transcription PCR

5-aza

5-Aza-2′-deoxycytidine

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Yuanzi Yu
    • 1
    • 2
  • Dongtao Yin
    • 3
  • Mohammad O. Hoque
    • 4
  • Baoping Cao
    • 1
    • 2
  • Yan Jia
    • 1
    • 2
  • Yunsheng Yang
    • 1
  • Mingzhou Guo
    • 1
  1. 1.Department of Gastroenterology and HepatologyChinese PLA General HospitalBeijingChina
  2. 2.Medical College of NanKai University300071China
  3. 3.Department of Cardiothoracic SurgerySecond Artillery Corps General HospitalBeijingChina
  4. 4.Department of Otolaryngology-Head and Neck Cancer, Research DivisionJohns Hopkins School of MedicineBaltimoreUSA