TGFBI is involved in the formation of polyploid cancer cells and the response to paclitaxel.
TGFBI is involved in the formation of polyploid cancer cells and the response to paclitaxel.
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DOI：
10.21037/atm-21-1698
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发表时间：
2021-04
影响因子：
--
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Shang X;Yuan B;Li J;Xi F;Mao J;Zhang C;Jiang H;Liu G
大多数人类实体瘤是非整倍体；同时，多倍体癌细胞被发现对放疗和化疗具有抵抗力，预后较差。转化生长因子β诱导（TGFBI）蛋白在肿瘤的发展中发挥着重要作用，具体取决于癌症的起源。在这项研究中，我们建立了用诺考达唑治疗的乳腺癌的多倍体克隆。采用MTT法测定药物敏感性。 Western blot分析检测多倍体克隆中TGFBI蛋白的表达。通过流式细胞术分析紫杉醇对细胞凋亡、细胞周期和DNA倍性的影响。通过免疫组织化学染色在上皮性卵巢肿瘤患者的样本中检测 TGFBI 蛋白的表达。我们发现与MDA-MB-231细胞系相比，HGF1806细胞系中TGFBI的表达相对较高。此外，与其亲本细胞相比，TGFBI在多倍体乳腺癌细胞系T-MDA-MB-231中表现出相对较低的表达。与空载体相比，紫杉醇处理下，TGFBI在MDA-MB-231和T-MDA-MB-231中过表达均表现出更高的生长抑制率。诺考达唑处理后，MDF-MB-231细胞中TGFBI过度表达，证明四倍体细胞的表达较对照较低。化疗前卵巢癌标本中TGFBI表达阳性率为33.3%（5/15），高于治疗后与复发标本匹配的卵巢癌标本中TGFBI表达阳性率（0%，0/15）。 TGFBI可增加多倍体癌细胞对紫杉醇的敏感性，并参与诺考达唑诱导的MDA-MB-231多倍体的形成。 TGFBI 的这一新认识的作用提供了对多倍体癌症发病机制的进一步了解，并确定了潜在的新治疗靶点。
Most human solid tumors are aneuploid; at the same time, polyploid cancer cells are found to be resistant to radiotherapy and chemotherapy and have a poor prognosis. The transforming growth factor beta induction (TGFBI) protein plays important roles in the development of tumors, depending on the cancer of origin. In this study, we established polyploid clones of breast cancer treated with nocodazole. The drug sensitivity was measured by MTT assay. Western blot analysis was used to detect the expression of TGFBI protein in polyploid clones. The effects of paclitaxel on apoptosis, cell cycle and DNA ploidy were analyzed by flow cytometry. TGFBI protein expression was performed in samples from patients with epithelial ovarian tumors by immunohistochemical staining. We found that compared with the MDA-MB-231 cell line, the expression of TGFBI in the HGF1806 cell line was relatively higher. In addition, compared with its parental cells, TGFBI showed relatively low expression in the polyploid breast cancer cell line T-MDA-MB-231. Compared with the empty vector, under paclitaxel treatment, the over-expression of TGFBI in MDA-MB-231 and T-MDA-MB-231 both showed a higher growth inhibition rate. After nocodazole treatment, the over-expression of TGFBI in MDF-MB-231 cells proved that the expression of tetraploid cells was lower compared to the control. The positive rate of TGFBI expression in ovarian cancer specimens before chemotherapy was 33.3% (5/15), which was higher than the positive rate of TGFBI expression in ovarian cancer specimens matched with relapsed specimens after treatment (0%, 0/15). TGFBI can increase the sensitivity of paclitaxel in polyploid cancer cells and participate in the formation of polyploidy in MDA-MB-231 induced by nocodazole. This newly recognized role of TGFBI provides further insight into the pathogenesis of polyploid cancer and identifies potential new therapeutic targets.
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影响因子：
50.3
作者：
Ahmed AA;Mills AD;Ibrahim AE;Temple J;Blenkiron C;Vias M;Massie CE;Iyer NG;McGeoch A;Crawford R;Nicke B;Downward J;Swanton C;Bell SD;Earl HM;Laskey RA;Caldas C;Brenton JD
通讯作者：
Brenton JD
TGFBI 缺乏使小鼠容易自发形成肿瘤。
影响因子：
11.2
作者：
Zhang Y;Wen G;Shao G;Wang C;Lin C;Fang H;Balajee AS;Bhagat G;Hei TK;Zhao Y
通讯作者：
Zhao Y
影响因子：
11.5
作者：
Etemadmoghadam, Dariush;Au-Yeung, George;Bowtell, David D.
通讯作者：
Bowtell, David D.
影响因子：
3.1
作者：
SKONIER, J;NEUBAUER, M;PURCHIO, AF
通讯作者：
PURCHIO, AF
影响因子：
4.6
作者：
Zhao, YL;El-Gabry, M;Hei, TK
通讯作者：
Hei, TK