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A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.

Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS - EMBO Mol Med (2012)

Bottom Line: Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease.Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women.We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

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The effect of the KRAS variant allele on proliferation and invasion capacity of hESCThe effect of the KRAS variant allele on proliferation of hESC from women with endometriosis as determined by BrdU incorporation. There was a 71% increase (*p = 0.04) in the BrdU label in hESC with the variant allele (n = 5) versus WT KRAS LCS6 (n = 5). These results indicated an increase in cell proliferation rate of hESC containing the mutant KRAS LCS6.The effect of the KRAS variant allele on hESC invasion capacity. An invasion assay in which hESC from women with and without endometriosis and with the WT non-variant or the alternative KRAS allele was used to determine the ability to invade extracellular matrix. There was a significant increase in the invasion of hESC containing the variant allele (n = 9) compared to hESC without the variant allele (n = 6) (*p = 0.013). The difference between normal cells (n = 6) and cells from endometriosis with WT KRAS was not significant.
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fig04: The effect of the KRAS variant allele on proliferation and invasion capacity of hESCThe effect of the KRAS variant allele on proliferation of hESC from women with endometriosis as determined by BrdU incorporation. There was a 71% increase (*p = 0.04) in the BrdU label in hESC with the variant allele (n = 5) versus WT KRAS LCS6 (n = 5). These results indicated an increase in cell proliferation rate of hESC containing the mutant KRAS LCS6.The effect of the KRAS variant allele on hESC invasion capacity. An invasion assay in which hESC from women with and without endometriosis and with the WT non-variant or the alternative KRAS allele was used to determine the ability to invade extracellular matrix. There was a significant increase in the invasion of hESC containing the variant allele (n = 9) compared to hESC without the variant allele (n = 6) (*p = 0.013). The difference between normal cells (n = 6) and cells from endometriosis with WT KRAS was not significant.

Mentions: We assessed proliferation in the presence of the KRAS LCS6 variant allele using BrdU labelling. This assay showed a 71% increase of BrdU labelling in KRAS LCS6 variant hESC, indicative of an increased proliferation rate of endometrial cells from women with the variant allele compared to those with the non-variant allele (absorbance 0.48 ± 0.08 vs. 0.28 ± 0.02; p = 0.04; Fig 4a).


A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.

Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS - EMBO Mol Med (2012)

The effect of the KRAS variant allele on proliferation and invasion capacity of hESCThe effect of the KRAS variant allele on proliferation of hESC from women with endometriosis as determined by BrdU incorporation. There was a 71% increase (*p = 0.04) in the BrdU label in hESC with the variant allele (n = 5) versus WT KRAS LCS6 (n = 5). These results indicated an increase in cell proliferation rate of hESC containing the mutant KRAS LCS6.The effect of the KRAS variant allele on hESC invasion capacity. An invasion assay in which hESC from women with and without endometriosis and with the WT non-variant or the alternative KRAS allele was used to determine the ability to invade extracellular matrix. There was a significant increase in the invasion of hESC containing the variant allele (n = 9) compared to hESC without the variant allele (n = 6) (*p = 0.013). The difference between normal cells (n = 6) and cells from endometriosis with WT KRAS was not significant.
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Related In: Results  -  Collection

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fig04: The effect of the KRAS variant allele on proliferation and invasion capacity of hESCThe effect of the KRAS variant allele on proliferation of hESC from women with endometriosis as determined by BrdU incorporation. There was a 71% increase (*p = 0.04) in the BrdU label in hESC with the variant allele (n = 5) versus WT KRAS LCS6 (n = 5). These results indicated an increase in cell proliferation rate of hESC containing the mutant KRAS LCS6.The effect of the KRAS variant allele on hESC invasion capacity. An invasion assay in which hESC from women with and without endometriosis and with the WT non-variant or the alternative KRAS allele was used to determine the ability to invade extracellular matrix. There was a significant increase in the invasion of hESC containing the variant allele (n = 9) compared to hESC without the variant allele (n = 6) (*p = 0.013). The difference between normal cells (n = 6) and cells from endometriosis with WT KRAS was not significant.
Mentions: We assessed proliferation in the presence of the KRAS LCS6 variant allele using BrdU labelling. This assay showed a 71% increase of BrdU labelling in KRAS LCS6 variant hESC, indicative of an increased proliferation rate of endometrial cells from women with the variant allele compared to those with the non-variant allele (absorbance 0.48 ± 0.08 vs. 0.28 ± 0.02; p = 0.04; Fig 4a).

Bottom Line: Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease.Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women.We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

Show MeSH
Related in: MedlinePlus