Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells

Takashi Nagashima, Tetsuo Maruyama, Hiroshi Uchida, Takashi Kajitani, Toru Arase, Masanori Ono, Hideyuki Oda, Maki Kagami, Hirotaka Masuda, Sayaka Uchida, Hironori Asada, Yasunori Yoshimura

Research output: Contribution to journalArticle

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Abstract

Progesterone induces decidual transformation of estrogen-primed human endometrial stromal cells (hESCs), critical for implantation and maintenance of pregnancy, through activation of many signaling pathways involving protein kinase A and signal transducer and activator of transcription (STAT)-5. We have previously shown that kinase activation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase is closely associated with decidualization and that SRC is indispensable for maximal decidualization in mice. To address whether SRC kinase activity is essential for decidualization in humans, hESCs were infected with adenoviruses carrying enhanced green fluorescent protein alone (Ad-EGFP), a kinase-inactive dominant-negative mutant (Ad-SRC/ K295R), or an inactive autophosphorylation site mutant (Ad-SRC/Y416F). The cells were cultured in the presence of estradiol and progesterone (EP) to induce decidualization and subjected to RT-PCR, immunoblot, and ELISA analyses. Ad-EGFP-infected hESCs exhibited decidual transformation and up-regulation of decidualization markers including IGF binding protein 1 and prolactin in response to 12-d treatment with EP. In contrast, hESCs infected with Ad-SRC/K295R remained morphologically fibroblastoid without production of IGF binding protein 1 and prolactin even after EP treatment. Ad-SRC/Y416F displayed similar but less inhibitory effects on decidualization, compared with Ad-SRC/K295R. During decidualization, STAT5 was phosphorylated on tyrosine 694, a well-known SRC phosphorylation site. Phosphorylation was markedly attenuated by Ad-SRC/K295R but not Ad-EGFP. These results indicate that the SRC-STAT5 pathway is essential for decidualization of hESCs.

Original languageEnglish
Pages (from-to)1227-1234
Number of pages8
JournalEndocrinology
Volume149
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Fingerprint

STAT5 Transcription Factor
Stromal Cells
Phosphotransferases
Phosphorylation
Progesterone
Adenoviridae
Insulin-Like Growth Factor Binding Protein 1
Estradiol
Prolactin
Pregnancy Maintenance
Cyclic AMP-Dependent Protein Kinases
Oncogenes
varespladib methyl
Sarcoma
Tyrosine
Cultured Cells
Estrogens
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. / Nagashima, Takashi; Maruyama, Tetsuo; Uchida, Hiroshi; Kajitani, Takashi; Arase, Toru; Ono, Masanori; Oda, Hideyuki; Kagami, Maki; Masuda, Hirotaka; Uchida, Sayaka; Asada, Hironori; Yoshimura, Yasunori.

In: Endocrinology, Vol. 149, No. 3, 03.2008, p. 1227-1234.

Research output: Contribution to journalArticle

Nagashima, Takashi ; Maruyama, Tetsuo ; Uchida, Hiroshi ; Kajitani, Takashi ; Arase, Toru ; Ono, Masanori ; Oda, Hideyuki ; Kagami, Maki ; Masuda, Hirotaka ; Uchida, Sayaka ; Asada, Hironori ; Yoshimura, Yasunori. / Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. In: Endocrinology. 2008 ; Vol. 149, No. 3. pp. 1227-1234.
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AU - Kajitani, Takashi

AU - Arase, Toru

AU - Ono, Masanori

AU - Oda, Hideyuki

AU - Kagami, Maki

AU - Masuda, Hirotaka

AU - Uchida, Sayaka

AU - Asada, Hironori

AU - Yoshimura, Yasunori

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