title: Overexpression and enhanced specific activity of aldoketo reductases (AKR1B1 & AKR1B10) in human breast cancers.
abstract: The incidence of breast cancer in India is on the rise and is rapidly becoming the primary cancer in Indian women. The aldoketo reductase (AKR) family has more than 190 proteins including aldose reductase (AKR1B1) and aldose reductase like protein (AKR1B10). Apart from liver cancer, the status of AKR1B1 and AKR1B10 with respect to their expression and activity has not been reported in other human cancers. We studied the specific activity and expression of AKR1B1 and AKR1B10 in breast non tumor and tumor tissues and in the blood. Fresh post-surgical breast cancer and non-cancer tissues and blood were collected from the subjects who were admitted for surgical therapy. Malignant, benign and pre-surgical chemotherapy samples were evaluated by histopathology scoring. Expression of AKR1B1 and AKR1B10 was carried out by immunoblotting and immunohistochemistry (IHC) while specific activity was determined spectrophotometrically. The specific activity of AKR1B1 was significantly higher in red blood cells (RBC) in all three grades of primary surgical and post-chemotherapy samples. Specific activity of both AKR1B1 and AKR1B10 increased in tumor samples compared to their corresponding non tumor samples (primary surgical and post-chemotherapy). Immunoblotting and IHC data also indicated overexpression of AKR1B1 in all grades of tumors compared to their corresponding non tumor samples. There was no change in the specific activity of AKR1B1 in benign samples compared to all grades of tumor and non-tumors.
authors.affiliation: National Institute of Nutrition, Hyderabad, India. Electronic address: geereddy@yahoo.com.
authors.forename: K Ashok
authors.initials: KA
authors.lastname: Reddy
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: P Uday
authors.initials: PU
authors.lastname: Kumar
authors.affiliation: MNJ Institute of Oncology, Hyderabad, India.
authors.forename: M
authors.initials: M
authors.lastname: Srinivasulu
authors.affiliation: MNJ Institute of Oncology, Hyderabad, India.
authors.forename: B
authors.initials: B
authors.lastname: Triveni
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: K
authors.initials: K
authors.lastname: Sharada
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Ismail
authors.affiliation: National Institute of Nutrition, Hyderabad, India. Electronic address: bhanu@icmr.org.in.
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000032:analysis / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D001940:Breast / Q000737:chemistry / Q000201:enzymology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000032:analysis; D060787:Neoplasm Grading; D011184:Postoperative Period; D057234:Preoperative Period; D051996:Transcription Factor RelA / Q000032:analysis; D051841:Transcription Factor RelB / Q000032:analysis; D055815:Young Adult
chemical_list: D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase
keywords: AKR1B1; AKR1B10; Aldose reductase; Breast cancer; Chemoresistance; Tumor grade