Prolactin-producing cells differentiate from G0/G1-arrested somatotrophs in vitro: an analysis of cell cycle phases and mammotroph differentiation.

Prolactin-producing cells differentiate from G0/G1-arrested somatotrophs in vitro: an analysis of cell cycle phases and mammotroph differentiation.
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催乳素产生细胞在体外与 G0/G1 停滞的生长激素细胞分化:细胞周期阶段和催乳素细胞分化的分析。

DOI:
10.1507/endocrj.45.725
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发表时间:
1998
期刊:
影响因子:
2
通讯作者:
Kinji Inoue
Kinji Inoue
中科院分区:
医学4区
文献类型:
--
作者:
H. Goda;Takafumi Sakai;M. Kurosumi;Kinji Inoue

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为了分析细胞增殖与乳腺增生分化之间的关系,我们研究了一株生长营养细胞系MtT/S。已知MtT/S细胞在胰岛素或胰岛素样生长因子-1 (IGF-1)刺激下分化为产生prl的细胞。标记增殖细胞的溴脱氧尿苷(BrdU)和GH或PRL的双重免疫染色显示,大多数BrdU标记的细胞是GH免疫阳性,而相当少的PRL阳性细胞被BrdU标记。用增殖细胞核抗原(PCNA)抗体对增殖细胞进行免疫染色证实了这一点。此外,流式细胞术分析显示,大多数产生prl的细胞处于细胞周期的G0/G1期。为了确定prl产生细胞的转分化是否需要细胞周期的改变,我们将MtT/S细胞在血清限制性培养基中培养7天,以降低其有丝分裂活性,然后用胰岛素和表皮生长因子(EGF)处理。在这些条件下,MtT/S细胞的细胞周期明显延迟,但诱导产生PRL的细胞百分比与对照条件几乎相同,表明产生PRL的细胞分化不需要有丝分裂。在胰岛素和EGF诱导产生prl的细胞过程中,我们还用BrdU标记MtT/S细胞24小时,结果发现BrdU标记的增殖细胞在产生prl的细胞群中特异性缺失。综上所述,PRL细胞是从G0/G1型生长因子中分化出来的,出现的PRL细胞的细胞增殖活性明显下降。综上所述,本文首次报道了PRL细胞的增殖与分化之间的关系。
In order to analyze the relationship between cell proliferation and mammotroph differentiation, we studied a somatotrophic cell line, MtT/S. MtT/S cell is known to differentiate into PRL-producing cells in response to stimulation with insulin or insulin-like growth factor-1 (IGF-1). Double immunostaining for bromodeoxyuridine (BrdU), which labels proliferating cells, and for GH or PRL showed that most BrdU-labeled cells were GH-immunopositive, whereas considerably few PRL-positive cells were labeled with BrdU. This was confirmed by immunostaining of proliferating cells with antibody to proliferating cell nuclear antigen (PCNA). Furthermore, flow-cytometry analysis indicated that most of the PRL-producing cells were in the G0/G1 phase of the cell cycle. In order to determine whether cell cycle changes are required for transdifferentiation of PRL-producing cells, MtT/S cells were cultivated in serum restricted medium for 7 days to reduce their mitotic activity and then treated with insulin and epidermal growth factor (EGF). Under these conditions, the cell cycle of MtT/S cells was significantly delayed, but the percentage of PRL-producing cells induced was almost identical to that under control conditions, showing that mitosis is not required for PRL- producing cell differentiation. We also labeled MtT/S cells with BrdU for 24 h during PRL-producing cell induction by insulin and EGF, and as a result BrdU-labeled proliferative cells were specifically absent from PRL-producing cell populations. These data, taken as whole, suggest that PRL cells differentiated from G0/G1 arrested somatotrophs and the PRL cells which appeared had their cell proliferation activity significantly declined. In conclusion, this is the first report showing the relationship cell between proliferation and differentiation of PRL cells.
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