Overexpression of aldo-keto reductase 1C2 is associated with disease progression in patients with prostatic cancer

Histopathology. 2010 Sep;57(3):384-94. doi: 10.1111/j.1365-2559.2010.03647.x.

Abstract

Aims: Prostatic cancer is resistant to chemotherapy. Expression of aldo-keto reductase 1C (AKR1C) has been associated with drug resistance and disease progression in several cancers. The aim was to investigate the relationship between AKR1C expression and disease progression in prostatic cancer.

Methods and results: From January 1996 to December 2005, 86 pathological samples were collected from patients with prostatic cancer. A tissue microarray containing 31 prostatic cancers from American patients was used for comparison between Chinese and American patients. Using immunohistochemistry, aldo-keto reductase family 1, member C2 (AKR1C2) expression was assessed in tissue sections. The AKR1C2 was determined by two-dimensional immunoblotting and DNA sequencing of reverse transcriptase-polymerase chain reaction products. The relationship between AKR1C2 expression and clinicopathological variables was statistically analysed. In vitro, the association between AKR1C2 expression and drug resistance was investigated in androgen-sensitive and androgen-insensitive prostatic cancer cells. DNA sequencing and two-dimensional immunoblotting showed that prostatic cancer expressed AKR1C2. It was overexpressed in 77 of 86 (89.5%) Chinese and in 28 of 31 (90.3%) American samples. No difference was found in AKR1C2 expression between Chinese and American prostatic cancer patients. In vitro, increased expression of AKR1C2 and prostaglandin F2α correlated with cytoprotection against anticancer drugs and lycopene.

Conclusion: Overexpression of AKR1C2 is associated with disease progression in prostatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Male
  • Middle Aged
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tumor Cells, Cultured

Substances

  • Receptors, Androgen
  • Hydroxysteroid Dehydrogenases
  • AKR1C2 protein, human