Transcription factor snail modulates hormone expression in established endocrine pancreatic cell lines.
The development of differentiated cells from undifferentiated progenitor cells is one of the central tenets of developmental biology. However, under conditions of tissue morphogenesis, regeneration, and cancer, this process of development is reversed and fully differentiated cells transition to an undifferentiated phenotype. Here we present evidence that the zinc-finger transcription factor Snail modulates this transition in differentiated pancreatic endocrine cell lines. During passage and growth of these cell lines, Snail expression is induced in a subset of cells within the culture, concomitant with a decrease in insulin and/or glucagon expression. As the cells cluster and exit the cell division cycle, nuclear levels of Snail are reduced and hormone expression is resumed. Snail represses proinsulin and proglucagon gene transcription, and reduction of Snail levels by small interfering RNA treatment increases proinsulin gene expression. We propose that Snail modulates the dynamic balance between differentiated and dedifferentiated cells allowing their migration and proliferation. These findings may be relevant to providing approaches for the enhancement of beta-cell growth in individuals with diabetes mellitus.
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02114, USA.
J Michael
JM
Rukstalis
Mariano
M
Ubeda
Megan V
MV
Johnson
Joel F
JF
Habener
D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D007328:Insulin; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D005934:Glucagon