Altered expression of the hormone- and xenobiotic-metabolizing sulfotransferase enzymes 1A2 and 1C1 in malignant breast tissue.
Cytosolic sulfotransferases (SULTs) catalyze the biotransformation of steroid hormones as well as drugs and environmental toxins. Mostly, sulfonation leads to an inactivation of parent compounds, although formation of more toxic and cancerogenic metabolites also occurs. To assess possible alterations in the SULT enzyme expression pattern between malignant and non-malignant tissue, we studied the presence of 9 SULT enzymes of family 1 and 2 by semi-quantitative RT-PCR. Forty-two specimens from ductal and lobular breast carcinomas, lymph node metastasis, mastopathy and normal breast tissue were derived from 29 patients. Substantial expression of SULT 1A1, 1A2, 1A3, 1B1, 1C1, 1E1, 2A1, 2B1a and 2B1b mRNAs was observed in malignant and non-malignant tissue, although the pattern of the individual SULTs varied between the patients, and SULT1C1 mRNA was present in a greater number of malignant than non-malignant tissues (p<0.05). A major finding was that unspliced SULT1A2 mRNA, containing the complete intron between exons 7 and 8, was found in 4 of 16 non-malignant specimens, but was undetectable in the 26 malignant samples investigated. Taken together, the presence of various SULT enzymes in normal, premalignant and malignant breast tissue suggests an important role of SULT-mediated biotransformation in the breast. While the increased expression of SULT1C1 in malignant tissue seems to reflect tumor dedifferentiation, our finding of unspliced SULT1A2 mRNA in non-malignant tissue offers additional aspects regarding the search for breast cancer risk factors.
Aust
Sylvia
S
Center for Physiology and Pathophysiology, Medical University of Vienna, AKH, Waehringer Guertel 18-20, A-1020 Vienna, Austria.
Obrist
Peter
P
Klimpfinger
Martin
M
Tucek
Gerhard
G
Jäger
Walter
W
Thalhammer
Theresia
T
D000368:Aged; D015239:Arylsulfotransferase / Q000096:biosynthesis*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D044584:Carcinoma, Ductal / Q000201:enzymology* / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000201:enzymology* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000494:pharmacology*; D015262:Xenobiotics / Q000378:metabolism
D015262:Xenobiotics; C513319:SULT1C2 protein, human; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C513290:SULT1A2 protein, human