Premium
Inhibition of prostate cancer metastatic colonization by ∼4.2 Mb of human chromosome 12
Author(s) -
Jaeger Erich B.,
Chekmareva Marina A.,
Tennant Thelma R.,
Luu Hue H.,
Hickson Jonathan A.,
Chen Stephen L.,
Samant Rajeev S.,
Sokoloff Mitchell H.,
RinkerSchaeffer Carrie W.
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11483
Subject(s) - metastasis suppressor gene , metastasis , metastasis suppressor , biology , cancer research , gene , tumor suppressor gene , cancer , prostate cancer , chromosome , suppressor , microbiology and biotechnology , genetics , carcinogenesis
Our previous studies demonstrate that introduction of a ∼70 cM region (now estimated at 63.75 Mb by the Human Genome Project) of human chromosome 12 into the highly metastatic Dunning rat prostate cancer cell line AT6.1 results in >30‐fold (≥90%) reduction in the number of overt metastases in spontaneous metastasis assays. We report the further localization and biological characterization of the metastasis‐suppressor activity encoded by a reduced region of chromosome 12. To localize this metastasis‐suppressor activity, a panel of AT6.1 microcell hybrids that retain varying portions of human chromosome 12 was constructed and subjected to sequence‐tagged site (STS)‐based PCR analysis and assessment of in vivo metastatic ability. Data from these complementary approaches localized the metastasis‐suppressor activity to a ∼4.2 Mb portion of human chromosome 12q24.3 comprised of 3 separate regions. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and immunoblotting were used for differential expression analyses to identify which characterized genes, predicted gene sequences and expressed sequence tags (ESTs) within this region could be responsible for the observed metastasis suppression. Comprehensive in vivo studies showed that suppressed AT6.1‐12 hybrids that retain the metastasis‐suppressor region on 12q24.3 are capable of arriving at the secondary site, but are not able to persist there. Thus, unlike other metastasis‐suppressor genes characterized to date, the metastasis‐suppressor gene encoded by this region appears to utilize a different biologic mechanism to suppress the growth of overt metastases at the secondary site. © 2003 Wiley‐Liss, Inc.