The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas

Carolina Gestblom, Anna Grynfeld, Ingrid Øra, Eva Örtoft, Christer Larsson, Håkan Axelson, Bengt Sandstedt, Peter Cserjesi, Eric N. Olson, Sven Påhlman

Research output: Contribution to journalArticle

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Abstract

Neuroblastoma is derived from the sympathetic nervous system and might arise as a result of impaired differentiation, retaining the neuroblastic tumor cells in the cell cycle. Thus, to understand the genesis of neuroblastoma, the study of mechanisms and genes regulating normal sympathetic development is of potential interest. The basic helix-loop-helix transcription factors human achaete-scute homolog-1 (HASH-1) and deciduum, heart, autonomic nervous system, and neural crest derivatives (dHAND) are expressed in the sympathetic nervous system of embryonic mice and chicken, with undetectable postnatal expression. By in situ hybridization technique, we show that dHAND was expressed by human sympathetic neuronal and extra- adrenal chromaffin cells throughout embryonic and fetal life, and was initially expressed in immature chromaffin cells of the adrenal gland. With overt chromaffin differentiation, dHAND was down-regulated. HASH-1, in contrast, was expressed in human sympathetic cells only at the earliest embryonic ages examined (Week 6.5 to 7). All examined neuroblastoma specimens (25/25) and all cell lines (5/5) had detectable dHAND mRNA levels. HASH-1 expression in tumor specimens was more restricted, although all cell lines (5/5) were HASH-1-positive. These results show that neuroblastoma tumors have retained embryonic features, suggesting that many neuroblastomas are blocked at an early stage of normal development when HASH-1 and dHAND are expressed. dHAND also appears to be a reliable and potentially useful clinical diagnostic marker for neuroblastoma, because expression was not dependent on tumor or differentiation stages and other pediatric tumors were dHAND- negative.

Original languageEnglish (US)
Pages (from-to)67-79
Number of pages13
JournalLaboratory Investigation
Volume79
Issue number1
StatePublished - Jan 1999

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Basic Helix-Loop-Helix Transcription Factors
Sympathetic Nervous System
Neuroblastoma
Genes
Chromaffin Cells
Neoplasms
Cell Line
Decidua
Neural Crest
Autonomic Nervous System
Human Development
Adrenal Glands
In Situ Hybridization
Chickens
Cell Cycle
Biomarkers
Pediatrics
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas. / Gestblom, Carolina; Grynfeld, Anna; Øra, Ingrid; Örtoft, Eva; Larsson, Christer; Axelson, Håkan; Sandstedt, Bengt; Cserjesi, Peter; Olson, Eric N.; Påhlman, Sven.

In: Laboratory Investigation, Vol. 79, No. 1, 01.1999, p. 67-79.

Research output: Contribution to journalArticle

Gestblom, C, Grynfeld, A, Øra, I, Örtoft, E, Larsson, C, Axelson, H, Sandstedt, B, Cserjesi, P, Olson, EN & Påhlman, S 1999, 'The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas', Laboratory Investigation, vol. 79, no. 1, pp. 67-79.
Gestblom, Carolina ; Grynfeld, Anna ; Øra, Ingrid ; Örtoft, Eva ; Larsson, Christer ; Axelson, Håkan ; Sandstedt, Bengt ; Cserjesi, Peter ; Olson, Eric N. ; Påhlman, Sven. / The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas. In: Laboratory Investigation. 1999 ; Vol. 79, No. 1. pp. 67-79.
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