SPONTANEOUS TRANSFORMATION AND PROGRESSION IN CELL LINES
SPONTANEOUS TRANSFORMATION AND PROGRESSION IN CELL LINES
批准号:
3164257
负责人:
HARRY RUBIN
金额:
$5.75万
依托单位国家:
美国
项目类别:
财政年份:
1979
资助国家:
美国
项目状态:
已结题
起止时间:
1979-08-01 至 1986-12-31
关键词:
atomic absorption spectrometry cations cell cycle cell differentiation cell growth regulation cell population study chemical reaction contact inhibition glucose hormone regulation /control mechanism magnesium membrane permeability neoplastic transformation nucleic acid inhibitor nutrient requirement nutrition related tag phosphorylation polysomes ribosomes tissue /cell culture uridine
中文摘要
肿瘤细胞的异质性似乎是肿瘤治疗的主要障碍
英文摘要
Heterogeneity of cells in tumors appears to be a major obstacle in the
successful treatment of cancer. It is also of importance in understanding
the progression of cells to autonomous growth including metastasis. The
highest estimates of the rate of variation responsible for heterogeneity
have been on the order of one heritable alteration per 105 cell
divisions. In the past year we were able to isolate five clones among the
progeny of a Balb/3T3 cell which had just undergone spontaneous
transformation and to characterize their properties. We found that each of
the clones could be distinguished from the others by morphology,
colony-forming efficiency in agar (CFEag), and rate of tumor formation in
nude mice. The implication of this finding is that cultured cells are so
unstable soon after transformation that essentially every cell may differ
from the others in one or more characteristics, i.e., that there is a truly
radical heterogeneity. We have also studied the evolution of further
changes in these properties among the five clonal populations over a
6-month period and conclude that the type of variation which led to the
initial differences among the clones could also be responsible for
continuing change akin to tumor progression. Since the frequency of this
type of variation is very high and involves several properties in a
quantitative but uncoordinated way, it is unlikely to be caused by
conventional genetic mutations. Rather, it is likely to be an epigenetic
event.
This type of variation is also likely to play a role in our second major
finding, which is that some properties of transformed cells are altered
during tumor formation in the nude mouse and again when the tumor cells are
cultured. The former contradicts the generally accepted view that cells
are not changed by passage through nude mice. We find our example, that a
decrease in CFEag of more than 100-fold, is frequently observed during
tumor formation. Cells from some tumors regain their original high CFEag
after repeated passaging in culture but others do not. That is, there is a
heterogeneity of response, some changes being stable and others unstable.
The evidence to date indicates the alterations in cells during tumor
formation and subsequent cultivation are basically epigenetic in nature and
similar in type to those described above which occur after transformation.
The results promise to provide new ground for understanding the origin and
progression of cancer. (J)
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会议论文
The Cell Biology of Cancer and Aging
-
批准号:6624381
-
项目类别:
-
资助金额:$5.62万
-
财政年份:2002
-
负责人:HARRY RUBIN
-
依托单位:
The Cell Biology of Cancer and Aging
-
批准号:6748460
-
项目类别:
-
资助金额:$5.9万
-
财政年份:2002
-
负责人:HARRY RUBIN
-
依托单位:
The Cell Biology of Cancer and Aging
-
批准号:6474324
-
项目类别:
-
资助金额:$5.33万
-
财政年份:2002
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164258
-
项目类别:
-
资助金额:$3.7万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164262
-
项目类别:
-
资助金额:$17.18万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164254
-
项目类别:
-
资助金额:$16.61万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
SPONTANEOUS TRANSFORMATION AND PROGRESSION IN CELL LINES
-
批准号:3164259
-
项目类别:
-
资助金额:$10.25万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164261
-
项目类别:
-
资助金额:$16.23万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164263
-
项目类别:
-
资助金额:$17.19万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY
-
批准号:3164260
-
项目类别:
-
资助金额:$15.76万
-
财政年份:1979
-
负责人:HARRY RUBIN
-
依托单位:
海外基金