Friday 7 December 2007
Uptake and export transporters SLCOs are involved in the removal of endogenous and xenobiotic substances from blood by the liver.
Human liver-specific organic anion transporter-2 (LST-2/OATP8/SLCO1B3) has been demonstrated to be expressed in various gastrointestinal carcinomas and also to play pivotal roles in the uptake of a wide variety of both endogenous and exogenous anionic compounds, including bile acids, conjugated steroids and hormones, into hepatocytes in the human liver. However, the biological significance of LST-2 in human carcinomas remains unknown.
Mammary carcinomas (breast cancer)
Considering that LST-2 transports estrone-3-sulfate, LST-2 overexpression is associated with a hormone-dependent growth mechanism of the breast cancer. LST-2 immunoreactivity is a potent prognostic factor in human breast cancer. (17760952)
Steroid hormones have been implicated in playing a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes or hormones involved in androgen regulatory pathway are proposed to influence an individual’s risk for developing prostate cancer.
Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival.
The SLCO1B3 or OATP1B3 (formerly OATP8) steroid uptake transporter is overexpressed in prostate cancer, and polymorphisms in SLCO1B3 have been associated with altered testosterone uptake, and also an increased prostate cancer risk.
Two polymorphic genetic markers in the SLCO1B3 (formerly SLC21A8) gene, called 334T>G and 699G>A have been identified, that can be measured in genomic DNA obtained from a blood sample to predict survival from diagnosis of prostate cancer in that individual patient.
This genetic profiling result has profound clinical applications in diagnosis for each individual patient and ultimate treatment regimen. A correlation between clinical outcome of SLCOlB3 genotype with median survival of androgen independent prostate cancer have been found.
The genotype is predictive of testosterone uptake through the OATP1B3 transporter, and this information is useful to inform clinical decisions regarding antiandrogen therapy.
SLCO1B3 genotyping can be used in combination on a gene chip with several polymorphisms known to predict survival of prostate cancer patients. Thus the OATP1B3 polymorphism would be one genetic marker in a series of other markers that would be used to inform clinical decisions. SLCO1B3 upregulation can be used as a prognostic tool.
Muto M, Onogawa T, Suzuki T, Ishida T, Rikiyama T, Katayose Y, Ohuchi N, Sasano H, Abe T, Unno M. Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma. Cancer Sci. 2007 Oct;98(10):1570-6. PMID: 17760952
Cui Y, König J, Nies AT, Pfannschmidt M, Hergt M, Franke WW, Alt W, Moll R, Keppler D.Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma.Lab Invest. 2003 Apr;83(4):527-38. PMID: 12695556