Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and 11.
Metastasis suppressor activities have previously been mapped to human chromosomes 17 and 11. Decreased expression of the metastasis suppressor gene NM23, which is located on chromosome 17, has been correlated with increased metastatic potential in mammary cancers. A region on human chromosome 11, from 11p11.2-p13, has been shown to suppress metastasis in rat prostatic carcinoma cells. In both cases the metastasis suppressor activity had no effect on tumorigenicity or tumor growth rate, demonstrating that the encoded activities are distinct from effects of tumor suppression. To determine whether these human chromosomes encode general or tissue-specific metastasis suppressor activities, a truncated human chromosome 17 (i.e., pter-q23) and a full-length human chromosome 11 were separately transferred into highly metastatic rat mammary and prostate cancer cell lines and tested for their ability to suppress spontaneous metastasis in vivo. These studies demonstrated that when the pter-q23 region of human chromosome 17 is retained by the microcell hybrids, the metastatic ability of both mammary and prostatic cancer cells is suppressed. In contrast, when the pter-q14 region of human chromosome 11 is retained, only the metastatic ability of prostatic cancer cells is suppressed. Additional studies demonstrated that the metastasis suppressor activity encoded by the chromosome 17 pter-q23 region is p53-independent and not due to enhanced expression of NM23 protein.
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
C W
CW
Rinker-Schaeffer
A L
AL
Hawkins
N
N
Ru
J
J
Dong
G
G
Stoica
C A
CA
Griffin
T
T
Ichikawa
J C
JC
Barrett
J T
JT
Isaacs
D000818:Animals; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D005260:Female; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics / Q000517:prevention & control*; D009701:Nucleoside-Diphosphate Kinase; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins