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Decreased expression of early growth response-1 and its role in uterine leiomyoma growth

SHOZU, Makio ; MURAKAMI, Kouichi ; SEGAWA, Tomoya ; KASAI, Tadayuki ; ISHIKAWA, Hiroshi ; SHINOHARA, Kazunori ; OKADA, Masahiko ; INOUE, Masaki

Cancer research (Chicago, Ill.), 2004-07, Vol.64 (13), p.4677-4684 [Periódico revisado por pares]

Philadelphia, PA: American Association for Cancer Research

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Título:
Decreased expression of early growth response-1 and its role in uterine leiomyoma growth
Autor: SHOZU, Makio ; MURAKAMI, Kouichi ; SEGAWA, Tomoya ; KASAI, Tadayuki ; ISHIKAWA, Hiroshi ; SHINOHARA, Kazunori ; OKADA, Masahiko ; INOUE, Masaki
Assuntos: Adult ; Antineoplastic agents ; Biological and medical sciences ; Cell Division - genetics ; DNA - metabolism ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; DNA-Binding Proteins - physiology ; Down-Regulation ; Early Growth Response Protein 1 ; Female ; Gene Expression Regulation, Neoplastic ; HMGA2 Protein - biosynthesis ; HMGA2 Protein - genetics ; Humans ; Immediate-Early Proteins - biosynthesis ; Immediate-Early Proteins - genetics ; Immediate-Early Proteins - metabolism ; Immediate-Early Proteins - physiology ; Leiomyoma - genetics ; Leiomyoma - metabolism ; Leiomyoma - pathology ; Medical sciences ; Middle Aged ; Muscle, Smooth - metabolism ; Pharmacology. Drug treatments ; Proto-Oncogene Proteins c-fos - biosynthesis ; Proto-Oncogene Proteins c-fos - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription Factors - physiology ; Transfection ; Tumors ; Uterine Neoplasms - genetics ; Uterine Neoplasms - metabolism ; Uterine Neoplasms - pathology ; Uterus - metabolism
É parte de: Cancer research (Chicago, Ill.), 2004-07, Vol.64 (13), p.4677-4684
Notas: ObjectType-Article-2
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Descrição: Expression of early growth response (Egr)-1, a transcriptional factor implicated in growth regulation, is suppressed in several malignant tumors. The present study investigated the expression of Egr-1 and related genes in uterine leiomyoma and normal myometrium to determine possible contributions of Egr-1 to neoplastic growth in leiomyoma cells. Levels of Egr-1 transcripts were decreased in all leiomyomas (n = 20) to approximately 10% of levels in corresponding myometrium, where basal expression was high. Preoperative leuprorelin acetate therapy increased levels of Egr-1 mRNA in normal myometrium only. Northern blot analysis using additional sample sets (n = 5) revealed the full-length Egr-1 transcript. Western blot analysis (n = 5) confirmed decreased expression of Egr-1 protein. Southern blot analysis of the Egr-1 gene and microsatellite analysis of the chromosomal location at 5q31 (D5S414, D5S500, and D5S476) revealed neither DNA recombination nor loss of heterozygosity in leiomyomas. Moreover, Egr-1 retained identical responsiveness to phorbol 12-myristate 13-acetate in primary cultures derived from both leiomyoma and normal tissues. Electrophoretic mobility shift analysis revealed that phorbol 12-myristate 13-acetate-induced Egr-1 in leiomyoma cells retained DNA binding ability. Egr-1 thus appears functionally intact in leiomyoma cells. Finally, consistent with the role of Egr-1 in growth inhibition, transfection of Egr-1 expression vector into a myometrial cell line (KW) that expresses low levels of Egr-1 and displays rapid growth inhibited thymidine uptake in these cells. Egr-1 may display tumor-suppressing activity and offers a potential target for leiomyoma management.
Editor: Philadelphia, PA: American Association for Cancer Research
Idioma: Inglês

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Decreased expression of early growth response-1 and its role in uterine leiomyoma growth

SHOZU, Makio ; MURAKAMI, Kouichi ; SEGAWA, Tomoya ; KASAI, Tadayuki ; ISHIKAWA, Hiroshi ; SHINOHARA, Kazunori ; OKADA, Masahiko ; INOUE, Masaki

Philadelphia, PA: American Association for Cancer Research

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