In:
Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 3, No. 12_Supplement ( 2010-12-01), p. A9-A9
Kurzfassung:
The UDP-glucuronosyltransferase (UGT) family of enzymes catalyzes the glucuronidation of a variety of endogenous compounds such as bilirubin and steroid hormones, as well as xenobiotics including chemotherapeutic agents and environmental carcinogens. Glucuronidation of these substrates inactivates them by making them more hydrophilic and easily excreted. UGTs are expressed primarily in the liver, but are also expressed in several extrahepatic tissues including prostate, breast, colon, lung, brain, kidney, bladder, and ovary. However, there have been no reports measuring UGTs in melanocytes or melanoma. We screened several primary melanocyte cultures from neonatal foreskin as well as several primary and metastatic melanoma cell lines for UGT expression by RT-PCR. Three UGT family members, UGT2B7, UGT2B10, and UGT2B15, were found to be expressed in melanocytes. Interestingly, of all the melanoma cell lines screened only WM115, a primary melanoma, had UGT expression. Again, only UGT2B7, UGT2B10, and UGT2B15 were detected. UGT expression was not detected in another primary melanoma cell line, WM3211, or in any metastatic melanoma cell line assayed suggesting that loss of UGT expression occurs during melanoma progression. Knockdown of UGT2B7 in WM115 cells using shRNA resulted in a 2.6-fold increase in invasiveness as measured by migration through Matrigel. Conversely, stable expression of UGT2B7 in the metastatic melanoma cell line SKmel28 (which lacks UGT expression) resulted in dramatic reduction of invasiveness. Furthermore, treatment of SKmel28 cells stably expressing UGT2B7 with β-estradiol (a competitive inhibitor of UGT2B7) restored invasiveness of this cell line to parental levels. Thus, glucuronidation prevents invasiveness in melanoma. Taken together, we hypothesize that the observed loss of UGT expression is required for melanoma progression and that preventing the loss of UGT expression may be a viable strategy for melanoma chemoprevention. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A9.
Materialart:
Online-Ressource
ISSN:
1940-6207
,
1940-6215
DOI:
10.1158/1940-6207.PREV-10-A9
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2010
ZDB Id:
2422346-3
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