TY - JOUR
T1 - Identification of a human achaete-scute homolog highly expressed in neuroendocrine tumors
AU - Ball, Douglas W.
AU - Azzoli, Christopher G.
AU - Baylin, Stephen B.
AU - Chi, David
AU - Dou, Shenshen
AU - Donis-Keller, Helen
AU - Cumaraswamy, Arunthathi
AU - Borges, Michael
AU - Nelkin, Barry D.
PY - 1993/6/15
Y1 - 1993/6/15
N2 - Basic helix-loop-helix transcription factors of the achaete-scute family are instrumental in Drosophila neurosensory development and are candidate regulators of development in the mammalian central nervous system and neural crest. We report the isolation and initial characterization of a human achaete-scute homolog that is highly expressed in two neuroendocrine cancers, medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). The human gene, which we have termed human achaete-scute homolog 1 (hASH1), was cloned from a human MTC cDNA library. It encodes a predicted protein of 238 aa that is 95% homologous to mammalian achaete-scute homolog (MASH) 1, a rodent basic helix-loop-helix factor. The 57-residue basic helix-loop-helix domain is identical to that in the rodent gene, and the basic and helical regions, excluding the loop, are 72-80% identical to Drosophila achaete-scute family members. The proximal coding region of the hASH1 cDNA contains a striking 14-copy repeat of the triplet CAG that exhibits polymorphism in human genomic DNA. Thus, hASH1 is a candidate locus for disease-causing mutations via triplet repeat amplification. Analysis of rodent-human somatic cell hybrids permitted assignment of hASH1 to human chromosome 12. Northern blots revealed hASH1 transcripts in RNA from a human MTC cell line, two fresh MTC tumors, fetal brain, and three lines of human SCLC. In contrast, cultured lines of non-SCLC lung cancers and a panel of normal adult human tissues showed no detectable hASH1 transcripts. Expression of hASH1 may provide a useful marker for cancers with neuroendocrine features and may contribute to the differentiation and growth regulation of these cells.
AB - Basic helix-loop-helix transcription factors of the achaete-scute family are instrumental in Drosophila neurosensory development and are candidate regulators of development in the mammalian central nervous system and neural crest. We report the isolation and initial characterization of a human achaete-scute homolog that is highly expressed in two neuroendocrine cancers, medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). The human gene, which we have termed human achaete-scute homolog 1 (hASH1), was cloned from a human MTC cDNA library. It encodes a predicted protein of 238 aa that is 95% homologous to mammalian achaete-scute homolog (MASH) 1, a rodent basic helix-loop-helix factor. The 57-residue basic helix-loop-helix domain is identical to that in the rodent gene, and the basic and helical regions, excluding the loop, are 72-80% identical to Drosophila achaete-scute family members. The proximal coding region of the hASH1 cDNA contains a striking 14-copy repeat of the triplet CAG that exhibits polymorphism in human genomic DNA. Thus, hASH1 is a candidate locus for disease-causing mutations via triplet repeat amplification. Analysis of rodent-human somatic cell hybrids permitted assignment of hASH1 to human chromosome 12. Northern blots revealed hASH1 transcripts in RNA from a human MTC cell line, two fresh MTC tumors, fetal brain, and three lines of human SCLC. In contrast, cultured lines of non-SCLC lung cancers and a panel of normal adult human tissues showed no detectable hASH1 transcripts. Expression of hASH1 may provide a useful marker for cancers with neuroendocrine features and may contribute to the differentiation and growth regulation of these cells.
KW - Basic helix-loop-helix protein
KW - Medullary thyroid carcinoma
KW - Small cell lung cancer
KW - Trinucleotide repeat
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U2 - 10.1073/pnas.90.12.5648
DO - 10.1073/pnas.90.12.5648
M3 - Article
C2 - 8390674
AN - SCOPUS:0027299597
SN - 0027-8424
VL - 90
SP - 5648
EP - 5652
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -