Oncogene amplification: Myc and neu oncoproteins

K. Saksela, P. Koskinen, H. Hirvonen, H. Lehväslaiho, T.P. Mäkelä, K. Alitalo

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Abstract

The first member of the myc gene family, the v-myc gene, was isolated from the avian myelocytomatosis virus MC29. 1-3 Its cellular homologue, the c-myc gene, is evolutionarily well conserved between different species.4-11 Two other closely related genes, N-myc and L-myc, have also been cloned and characterized. 12-19 The N-myc gene was isolated from a human neuroblastoma cell line,12 and the L-myc gene from a human small cell lung cancer (SCLC) cell line,13 where they appeared amplified. The c-myc, N-myc, and L-myc genes all consist of three exons which are located within less than 7 kb in distinct chromosomal regions 8q24,20 2p23-24,21 and Ip32,22 respectively. In contrast to the protein-coding sequences, the long noncoding portions of the corresponding mRNAs are not well conserved between the different myc genes. In addition, there are considerable differences in the regulatory regions of these genes.6.18.23.24 The myc gene family appears to contain at least three other functional members, the P-, R-, and B-myc genes, as well as an inactive pseudogene, L-myc ‘I’.25,26 The c-myc, N-myc, and L-myc genes have all been found to be amplified in human tumors. Amplifications of the c-myc gene are most common among the three genes, and are particularly frequent in SCLC cell lines13.27-30 and in breast cancer. 3 N-myc amplifications are common in neuroblastoma,15.32 SCLC,37 and retinoblastoma,33 Cases of N-myc amplification have also been detected in adenocarcinoma of the lung,34 astrocytoma,35 and rhabdomyosarcoma,36 L-myc amplifications have so far been discovered only in SCLC.29,37,38 Altogether, 35 to 40% ofestablished SCLC cell lines have amplified one of the three members of the myc gene family. It is also curious that in cell lines established from other types of human lung cancer, amplification of only c-myc has been detected. 39-41 Amplifications usually lead to enhanced myc mRNA and protein expression. 27 Some reports indicate that amplification of the c-myc gene correlates with the phenotypic properties of the corresponding cells. 29 ,42,43 The so-called variant SCLC cell lines carrying an amplified c-myc gene grow faster, more loosely aggregated, and they have an increased cloning efficiency when compared to typical SCLC lines. Curiously, contrary to the resuls from cell lines, c-myc amplifications are not very common in primary SCLC tumors. 34,38,44-47 This could suggest a role for c-myc amplification as a relatively late event during tumor progression, or indicate a selection for c-myc amplified cell clones during the establishment of continuously growing cell lines. Nonetheless, the basis for the discrepancy between the in vitro and the in vivo situation remains to be determined. © 1991 by CRC Press, Inc.
Original languageEnglish
Title of host publicationGrowth Regulation and Carcinogenesis
EditorsWalter R. Paukovits
Volume1
Place of PublicationBoca Raton
PublisherCRC Press
Publication date2018
Pages153-174
ISBN (Electronic)9781351080774
DOIs
Publication statusPublished - 2018
MoE publication typeA3 Book chapter

Fields of Science

  • 3122 Cancers
  • 3111 Biomedicine

Cite this

Saksela, K., Koskinen, P., Hirvonen, H., Lehväslaiho, H., Mäkelä, T. P., & Alitalo, K. (2018). Oncogene amplification: Myc and neu oncoproteins. In W. R. Paukovits (Ed.), Growth Regulation and Carcinogenesis (Vol. 1, pp. 153-174). Boca Raton: CRC Press. https://doi.org/10.1201/9781351072328
Saksela, K. ; Koskinen, P. ; Hirvonen, H. ; Lehväslaiho, H. ; Mäkelä, T.P. ; Alitalo, K. / Oncogene amplification: Myc and neu oncoproteins. Growth Regulation and Carcinogenesis. editor / Walter R. Paukovits. Vol. 1 Boca Raton : CRC Press, 2018. pp. 153-174
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abstract = "The first member of the myc gene family, the v-myc gene, was isolated from the avian myelocytomatosis virus MC29. 1-3 Its cellular homologue, the c-myc gene, is evolutionarily well conserved between different species.4-11 Two other closely related genes, N-myc and L-myc, have also been cloned and characterized. 12-19 The N-myc gene was isolated from a human neuroblastoma cell line,12 and the L-myc gene from a human small cell lung cancer (SCLC) cell line,13 where they appeared amplified. The c-myc, N-myc, and L-myc genes all consist of three exons which are located within less than 7 kb in distinct chromosomal regions 8q24,20 2p23-24,21 and Ip32,22 respectively. In contrast to the protein-coding sequences, the long noncoding portions of the corresponding mRNAs are not well conserved between the different myc genes. In addition, there are considerable differences in the regulatory regions of these genes.6.18.23.24 The myc gene family appears to contain at least three other functional members, the P-, R-, and B-myc genes, as well as an inactive pseudogene, L-myc ‘I’.25,26 The c-myc, N-myc, and L-myc genes have all been found to be amplified in human tumors. Amplifications of the c-myc gene are most common among the three genes, and are particularly frequent in SCLC cell lines13.27-30 and in breast cancer. 3 N-myc amplifications are common in neuroblastoma,15.32 SCLC,37 and retinoblastoma,33 Cases of N-myc amplification have also been detected in adenocarcinoma of the lung,34 astrocytoma,35 and rhabdomyosarcoma,36 L-myc amplifications have so far been discovered only in SCLC.29,37,38 Altogether, 35 to 40{\%} ofestablished SCLC cell lines have amplified one of the three members of the myc gene family. It is also curious that in cell lines established from other types of human lung cancer, amplification of only c-myc has been detected. 39-41 Amplifications usually lead to enhanced myc mRNA and protein expression. 27 Some reports indicate that amplification of the c-myc gene correlates with the phenotypic properties of the corresponding cells. 29 ,42,43 The so-called variant SCLC cell lines carrying an amplified c-myc gene grow faster, more loosely aggregated, and they have an increased cloning efficiency when compared to typical SCLC lines. Curiously, contrary to the resuls from cell lines, c-myc amplifications are not very common in primary SCLC tumors. 34,38,44-47 This could suggest a role for c-myc amplification as a relatively late event during tumor progression, or indicate a selection for c-myc amplified cell clones during the establishment of continuously growing cell lines. Nonetheless, the basis for the discrepancy between the in vitro and the in vivo situation remains to be determined. {\circledC} 1991 by CRC Press, Inc.",
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Saksela, K, Koskinen, P, Hirvonen, H, Lehväslaiho, H, Mäkelä, TP & Alitalo, K 2018, Oncogene amplification: Myc and neu oncoproteins. in WR Paukovits (ed.), Growth Regulation and Carcinogenesis. vol. 1, CRC Press, Boca Raton, pp. 153-174. https://doi.org/10.1201/9781351072328

Oncogene amplification: Myc and neu oncoproteins. / Saksela, K.; Koskinen, P.; Hirvonen, H.; Lehväslaiho, H.; Mäkelä, T.P.; Alitalo, K.

Growth Regulation and Carcinogenesis. ed. / Walter R. Paukovits. Vol. 1 Boca Raton : CRC Press, 2018. p. 153-174.

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

TY - CHAP

T1 - Oncogene amplification: Myc and neu oncoproteins

AU - Saksela, K.

AU - Koskinen, P.

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AU - Mäkelä, T.P.

AU - Alitalo, K.

PY - 2018

Y1 - 2018

N2 - The first member of the myc gene family, the v-myc gene, was isolated from the avian myelocytomatosis virus MC29. 1-3 Its cellular homologue, the c-myc gene, is evolutionarily well conserved between different species.4-11 Two other closely related genes, N-myc and L-myc, have also been cloned and characterized. 12-19 The N-myc gene was isolated from a human neuroblastoma cell line,12 and the L-myc gene from a human small cell lung cancer (SCLC) cell line,13 where they appeared amplified. The c-myc, N-myc, and L-myc genes all consist of three exons which are located within less than 7 kb in distinct chromosomal regions 8q24,20 2p23-24,21 and Ip32,22 respectively. In contrast to the protein-coding sequences, the long noncoding portions of the corresponding mRNAs are not well conserved between the different myc genes. In addition, there are considerable differences in the regulatory regions of these genes.6.18.23.24 The myc gene family appears to contain at least three other functional members, the P-, R-, and B-myc genes, as well as an inactive pseudogene, L-myc ‘I’.25,26 The c-myc, N-myc, and L-myc genes have all been found to be amplified in human tumors. Amplifications of the c-myc gene are most common among the three genes, and are particularly frequent in SCLC cell lines13.27-30 and in breast cancer. 3 N-myc amplifications are common in neuroblastoma,15.32 SCLC,37 and retinoblastoma,33 Cases of N-myc amplification have also been detected in adenocarcinoma of the lung,34 astrocytoma,35 and rhabdomyosarcoma,36 L-myc amplifications have so far been discovered only in SCLC.29,37,38 Altogether, 35 to 40% ofestablished SCLC cell lines have amplified one of the three members of the myc gene family. It is also curious that in cell lines established from other types of human lung cancer, amplification of only c-myc has been detected. 39-41 Amplifications usually lead to enhanced myc mRNA and protein expression. 27 Some reports indicate that amplification of the c-myc gene correlates with the phenotypic properties of the corresponding cells. 29 ,42,43 The so-called variant SCLC cell lines carrying an amplified c-myc gene grow faster, more loosely aggregated, and they have an increased cloning efficiency when compared to typical SCLC lines. Curiously, contrary to the resuls from cell lines, c-myc amplifications are not very common in primary SCLC tumors. 34,38,44-47 This could suggest a role for c-myc amplification as a relatively late event during tumor progression, or indicate a selection for c-myc amplified cell clones during the establishment of continuously growing cell lines. Nonetheless, the basis for the discrepancy between the in vitro and the in vivo situation remains to be determined. © 1991 by CRC Press, Inc.

AB - The first member of the myc gene family, the v-myc gene, was isolated from the avian myelocytomatosis virus MC29. 1-3 Its cellular homologue, the c-myc gene, is evolutionarily well conserved between different species.4-11 Two other closely related genes, N-myc and L-myc, have also been cloned and characterized. 12-19 The N-myc gene was isolated from a human neuroblastoma cell line,12 and the L-myc gene from a human small cell lung cancer (SCLC) cell line,13 where they appeared amplified. The c-myc, N-myc, and L-myc genes all consist of three exons which are located within less than 7 kb in distinct chromosomal regions 8q24,20 2p23-24,21 and Ip32,22 respectively. In contrast to the protein-coding sequences, the long noncoding portions of the corresponding mRNAs are not well conserved between the different myc genes. In addition, there are considerable differences in the regulatory regions of these genes.6.18.23.24 The myc gene family appears to contain at least three other functional members, the P-, R-, and B-myc genes, as well as an inactive pseudogene, L-myc ‘I’.25,26 The c-myc, N-myc, and L-myc genes have all been found to be amplified in human tumors. Amplifications of the c-myc gene are most common among the three genes, and are particularly frequent in SCLC cell lines13.27-30 and in breast cancer. 3 N-myc amplifications are common in neuroblastoma,15.32 SCLC,37 and retinoblastoma,33 Cases of N-myc amplification have also been detected in adenocarcinoma of the lung,34 astrocytoma,35 and rhabdomyosarcoma,36 L-myc amplifications have so far been discovered only in SCLC.29,37,38 Altogether, 35 to 40% ofestablished SCLC cell lines have amplified one of the three members of the myc gene family. It is also curious that in cell lines established from other types of human lung cancer, amplification of only c-myc has been detected. 39-41 Amplifications usually lead to enhanced myc mRNA and protein expression. 27 Some reports indicate that amplification of the c-myc gene correlates with the phenotypic properties of the corresponding cells. 29 ,42,43 The so-called variant SCLC cell lines carrying an amplified c-myc gene grow faster, more loosely aggregated, and they have an increased cloning efficiency when compared to typical SCLC lines. Curiously, contrary to the resuls from cell lines, c-myc amplifications are not very common in primary SCLC tumors. 34,38,44-47 This could suggest a role for c-myc amplification as a relatively late event during tumor progression, or indicate a selection for c-myc amplified cell clones during the establishment of continuously growing cell lines. Nonetheless, the basis for the discrepancy between the in vitro and the in vivo situation remains to be determined. © 1991 by CRC Press, Inc.

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BT - Growth Regulation and Carcinogenesis

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Saksela K, Koskinen P, Hirvonen H, Lehväslaiho H, Mäkelä TP, Alitalo K. Oncogene amplification: Myc and neu oncoproteins. In Paukovits WR, editor, Growth Regulation and Carcinogenesis. Vol. 1. Boca Raton: CRC Press. 2018. p. 153-174 https://doi.org/10.1201/9781351072328