Abstract
The development and progression of malignant tumors likely result from consecutive accumulation of genetic alterations, including dysfunctional tumor suppressor genes. However, the signaling mechanisms that underlie the development of tumors have not yet been completely elucidated. Discovery of novel tumor-related genes plays a crucial role in our understanding of the development and progression of malignant tumors. Chromosome engineering technology based on microcell-mediated chromosome transfer (MMCT) is an effective approach for identification of tumor suppressor genes. The studies have revealed at least five tumor suppression effects. The discovery of novel tumor suppressor genes provide greater understanding of the complex signaling pathways that underlie the development and progression of malignant tumors. These advances are being exploited to develop targeted drugs and new biological therapies for cancer.
Highlights
The appearance of frequency revertant microcell hybrid that have or escaped from suppression effects occurs at a fixed revertantcultures, microcell hybrid cells that have escaped fromsuppressor suppression effects at a fixedon frequency in late-passages resulting in loss of tumor genesoccurs or regions the introduced in late-passages cultures, resulting in loss of tumor suppressor genes or regions on the introduced chromosome
We previously identified the presence of senescence-related gene(s) in a 450- to 600-kb region on human chromosome 1q42.3 using a combination of functional analysis using sub-chromosomal transferrable fragments (STFs) in the mouse melanoma cell line B16-F10 and deletion mapping of revertant clones that escaped from cellular senescence [38]
We reported that introduction of human chromosome 3 using microcell-mediated chromosome transfer (MMCT) represses Human telomerase reverse transcriptase (hTERT) transcription in human renal carcinoma RCC23 cells with telomerase activity, resulting in induction of cellular senescence
Summary
Clones cancers, suggesting that several tumor suppressor genes are present on various chromosomes and Introduction of many human chromosomes can suppress the transformed phenotype of various play a crucial rolesuggesting in the development or progression of cancer. The appearance of cancers, that several tumor suppressor genes are present and play a crucial role incells the development progression of cancer. Investigation of common deleted regions in revertant microcell chromosome (Figure 3a). We previously identified the presence of senescence-related gene(s) in a 450- to 600-kb region on human chromosome 1q42.3 using a combination of functional analysis using STFs in the mouse melanoma cell line B16-F10 and deletion mapping of revertant clones that escaped from cellular senescence [38]. We provided evidence that functional STFs are useful for identification of the region on the chromosome that contains a tumor suppressor gene
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