Melanoma metastasis suppression by chromosome 6: Evidence for a pathway regulated by CRSP3 and TXNIP

Steven F. Goldberg, Mary E. Miele, Naohito Hatta, Minoru Takata, Carrie Paquette-Straub, Leonard P. Freedman, Danny R. Welch

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Loss of genetic material on chromosome 6 has been associated with progression of human melanomas. We showed previously that introducing chromosome 6 into metastatic human melanoma cell lines suppresses metastasis without affecting the ability of the hybrids to form progressively growing tumors. By subtractive hybridization comparing nonmetastatic chromosome 6-containing (neo6/C8161) versus parental (C8161) metastatic cells, the KISS1 metastasis suppressor gene was isolated. However, KISS1 mapped to chromosome 1q32. To identify upstream regulator(s) of (and downstream effectors of) KISS1, microarray hybridization comparing C8161 and neo6/C8161 variants was performed. TXNIP/VDUP1, a thioredoxin-binding protein, was expressed more highly in neo6/C8161 and in nonmetastatic melanomas. Increased TXNIP expression inhibited metastasis and up-regulated KISS1. Surprisingly, TXNIP also mapped to chromosome 1q. PCR karyotyping that refined the region on chromosome 6 identified CRSP3/DRIP130, a transcriptional coactivator, as a metastasis suppressor. CRSP3 transfectant cells had up-regulated KISS1 and TXNIP expression and were suppressed for metastasis. Quantitative real-time reverse-transcription PCR of clinical melanoma samples showed that loss of CRSP3 expression correlated with decreased KISS1 expression and increased metastasis. Thus, we implicated a specific gene on chromosome 6 in the etiology of melanoma metastasis and identified potential up-stream regulators of KISS1 and TXNIP.

Original languageEnglish (US)
Pages (from-to)432-440
Number of pages9
JournalCancer Research
Volume63
Issue number2
StatePublished - Jan 15 2003

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Chromosomes, Human, Pair 6
Melanoma
Neoplasm Metastasis
Chromosomes
Karyotyping
Polymerase Chain Reaction
Thioredoxins
Tumor Suppressor Genes
Genes
Reverse Transcription
Carrier Proteins
Cell Line
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Goldberg, S. F., Miele, M. E., Hatta, N., Takata, M., Paquette-Straub, C., Freedman, L. P., & Welch, D. R. (2003). Melanoma metastasis suppression by chromosome 6: Evidence for a pathway regulated by CRSP3 and TXNIP. Cancer Research, 63(2), 432-440.
Goldberg, Steven F. ; Miele, Mary E. ; Hatta, Naohito ; Takata, Minoru ; Paquette-Straub, Carrie ; Freedman, Leonard P. ; Welch, Danny R. / Melanoma metastasis suppression by chromosome 6 : Evidence for a pathway regulated by CRSP3 and TXNIP. In: Cancer Research. 2003 ; Vol. 63, No. 2. pp. 432-440.
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abstract = "Loss of genetic material on chromosome 6 has been associated with progression of human melanomas. We showed previously that introducing chromosome 6 into metastatic human melanoma cell lines suppresses metastasis without affecting the ability of the hybrids to form progressively growing tumors. By subtractive hybridization comparing nonmetastatic chromosome 6-containing (neo6/C8161) versus parental (C8161) metastatic cells, the KISS1 metastasis suppressor gene was isolated. However, KISS1 mapped to chromosome 1q32. To identify upstream regulator(s) of (and downstream effectors of) KISS1, microarray hybridization comparing C8161 and neo6/C8161 variants was performed. TXNIP/VDUP1, a thioredoxin-binding protein, was expressed more highly in neo6/C8161 and in nonmetastatic melanomas. Increased TXNIP expression inhibited metastasis and up-regulated KISS1. Surprisingly, TXNIP also mapped to chromosome 1q. PCR karyotyping that refined the region on chromosome 6 identified CRSP3/DRIP130, a transcriptional coactivator, as a metastasis suppressor. CRSP3 transfectant cells had up-regulated KISS1 and TXNIP expression and were suppressed for metastasis. Quantitative real-time reverse-transcription PCR of clinical melanoma samples showed that loss of CRSP3 expression correlated with decreased KISS1 expression and increased metastasis. Thus, we implicated a specific gene on chromosome 6 in the etiology of melanoma metastasis and identified potential up-stream regulators of KISS1 and TXNIP.",
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Goldberg, SF, Miele, ME, Hatta, N, Takata, M, Paquette-Straub, C, Freedman, LP & Welch, DR 2003, 'Melanoma metastasis suppression by chromosome 6: Evidence for a pathway regulated by CRSP3 and TXNIP', Cancer Research, vol. 63, no. 2, pp. 432-440.

Melanoma metastasis suppression by chromosome 6 : Evidence for a pathway regulated by CRSP3 and TXNIP. / Goldberg, Steven F.; Miele, Mary E.; Hatta, Naohito; Takata, Minoru; Paquette-Straub, Carrie; Freedman, Leonard P.; Welch, Danny R.

In: Cancer Research, Vol. 63, No. 2, 15.01.2003, p. 432-440.

Research output: Contribution to journalArticle

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AU - Goldberg, Steven F.

AU - Miele, Mary E.

AU - Hatta, Naohito

AU - Takata, Minoru

AU - Paquette-Straub, Carrie

AU - Freedman, Leonard P.

AU - Welch, Danny R.

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N2 - Loss of genetic material on chromosome 6 has been associated with progression of human melanomas. We showed previously that introducing chromosome 6 into metastatic human melanoma cell lines suppresses metastasis without affecting the ability of the hybrids to form progressively growing tumors. By subtractive hybridization comparing nonmetastatic chromosome 6-containing (neo6/C8161) versus parental (C8161) metastatic cells, the KISS1 metastasis suppressor gene was isolated. However, KISS1 mapped to chromosome 1q32. To identify upstream regulator(s) of (and downstream effectors of) KISS1, microarray hybridization comparing C8161 and neo6/C8161 variants was performed. TXNIP/VDUP1, a thioredoxin-binding protein, was expressed more highly in neo6/C8161 and in nonmetastatic melanomas. Increased TXNIP expression inhibited metastasis and up-regulated KISS1. Surprisingly, TXNIP also mapped to chromosome 1q. PCR karyotyping that refined the region on chromosome 6 identified CRSP3/DRIP130, a transcriptional coactivator, as a metastasis suppressor. CRSP3 transfectant cells had up-regulated KISS1 and TXNIP expression and were suppressed for metastasis. Quantitative real-time reverse-transcription PCR of clinical melanoma samples showed that loss of CRSP3 expression correlated with decreased KISS1 expression and increased metastasis. Thus, we implicated a specific gene on chromosome 6 in the etiology of melanoma metastasis and identified potential up-stream regulators of KISS1 and TXNIP.

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Goldberg SF, Miele ME, Hatta N, Takata M, Paquette-Straub C, Freedman LP et al. Melanoma metastasis suppression by chromosome 6: Evidence for a pathway regulated by CRSP3 and TXNIP. Cancer Research. 2003 Jan 15;63(2):432-440.