Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.
Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.
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DOI：
10.1002/cam4.251
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发表时间：
2014-08
期刊：
影响因子：
4
通讯作者：
Lin, Henry J.
中科院分区：
文献类型：
--
作者：
Tippin, Brigette L.;Kwong, Alan M.;Inadomi, Michael J.;Lee, Oliver J.;Park, Jae Man;Materi, Alicia M.;Buslon, Virgilio S.;Lin, Amy M.;Kudo, Lili C.;Karsten, Stanislav L.;French, Samuel W.;Narumiya, Shuh;Urade, Yoshihiro;Salido, Eduardo;Lin, Henry J.
关键词：
我们早期的研究表明，在ApcMin/+小鼠中，敲除造血前列腺素D合成酶（HPGDS，一种产生前列腺素D2的酶）会导致更多的腺瘤。相反，高表达的转基因HPGDS允许较少的肿瘤。前列腺素D2 （PGD2）与前列腺素D2受体PTGDR（或DP1）结合。PGD2代谢产物结合过氧化物酶体增殖物激活受体γ (PPARG)。我们假设Ptgdr或Pparg敲除可能会增加肿瘤数量，如果这些受体参与PGD2的肿瘤抑制。为了评估，我们制作了带有和不带有Ptgdr基因敲除的ApcMin/+小鼠（147只小鼠）。在单独的实验中，我们产生了表达转基因脂钙素型前列腺素D合成酶（PTGDS）的ApcMin/+小鼠，有和没有杂合Pparg敲除（104只小鼠）。纯合子Ptgdr敲除在6周和14周时使肿瘤总数增加30-40%。结肠肿瘤未受影响。单独杂合Pparg敲除不影响ApcMin/+小鼠的肿瘤数量。如上所述，我们的Pparg敲除评估也包括高表达PTGDS转基因的小鼠。携带转基因PTGDS的ApcMin/+小鼠的大腺瘤较少（为对照组的63%），结肠中v-myc禽髓细胞瘤病毒癌基因同源物（MYC） mRNA水平较低。杂合Pparg敲除似乎减弱了转基因PTGDS的肿瘤抑制作用。然而，在我们的实验中，PGD2的肿瘤抑制更明显是由受体PTGDR介导的。抑制机制似乎不涉及微血管密度的改变或肿瘤细胞增殖的减慢。这些数据支持PGD2信号通过PTGDR抑制肠道肿瘤的作用。
Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in ApcMin/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced ApcMin/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced ApcMin/+ mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in ApcMin/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. ApcMin/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.
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DOI：
10.1080/01635581.2011.590266
发表时间：
2011-08-01
影响因子：
2.9
作者：
Kwong, Alan M.;Tippin, Brigette L.;Lin, Henry J.
通讯作者：
Lin, Henry J.
影响因子：
6.4
作者：
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影响因子：
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作者：
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DOI：
10.3233/clo-2009-0458
发表时间：
2009
期刊：
Cellular oncology : the official journal of the International Society for Cellular Oncology
影响因子：
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作者：
Galamb O;Sipos F;Spisák S;Galamb B;Krenács T;Valcz G;Tulassay Z;Molnár B
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Molnár B
影响因子：
3.2
作者：
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Christoffels, VM