Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as a critical enzyme in reducing 5α-dihydrotestosterone (5α-DHT) to 5α-androstane-3α,17β-diol (3α-diol) and oxidizing 3α-diol to androsterone. Based on these enzymatic activities, AKR1C3 was originally named type 2 3α-hydroxysteroid dehydrogenase (HSD)/type 5 17β-HSD. Additionally, AKR1C3 was demonstrated to be capable of metabolizing other steroids including estrogen and progesterone. Subsequently, AKR1C3 was shown to possess 11-ketoprostaglandin reductase activity in metabolizing prostaglandins and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. Tissue distribution of AKR1C3 has been detected in both sex hormone-dependent organs such as the testis, breast, endometrium, and prostate as well as sex hormone-independent organs including the kidney and urothelium. Although prominent expression of AKR1C isozymes has been reported in human non-small cell lung carcinoma (NSCLC), the expression of AKR1C3 in small cell carcinoma of the lung has not been described. Also, the expression of AKR1C3 in normal lung has not been described. In this study, we demonstrated strong AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes. Strong AKR1C3 immunoreactivity was also demonstrated in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction. Although AKR1C3 immunoreactivity was absent in small cell carcinoma of the lung, positive AKR1C3 immunoreactivity was extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. AKR1C3 may serve as an adjunct marker for differentiating small cell carcinoma from NSCLC. However, roles of AKR1C3 in adenocarcinoma, squamous cell carcinoma, and small cell carcinoma pathogenesis require further studies.
College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Valerie L
VL
Miller
Hsueh-Kung
HK
Lin
Paari
P
Murugan
Michael
M
Fan
Trevor M
TM
Penning
Lacy S
LS
Brame
Qing
Q
Yang
Kar-Ming
KM
Fung
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074425:Aldo-Keto Reductase Family 1 Member C3; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004943:Esophagogastric Junction / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009825:Oklahoma; D011237:Predictive Value of Tests; D055752:Small Cell Lung Carcinoma / Q000201:enzymology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology
D014408:Biomarkers, Tumor; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3