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Published on: February 8, 2013
Alteration in gene expression at the onset of hormone-dependent mammary tumor regression
Abstract:
Two hormone-dependent mammary carcinomas regressing after hormone removal, [one primary 7,12-dimethylbenz(alpha)-anthracene induced, and the other transplanted MTW9] were used as models to test the hypothesis that the regression of hormone-dependent mammary tumors is triggered by a modification of the genetic expression. In support of the hypothesis, we observed that: (1) the in vitro translation products of poly(A)+ RNAs differ between growing and regressing tumors; (b) the difference is localized in four protein bands (mr 53,000, 35,000, 22,000 and 20,000) of the electrophoretic pattern that decrease in their concentrations and one protein band (Mr 20,500) that increases during regression; (c) the changes in the translation products occur within 6 hr post-hormone removal, and the changes are reversed when resumption of tumor growth was induced by replenishment of the hormone to the host rats: and (d) three autonomously growing tumors exhibit a unique translation pattern which differs from that of hormone-dependent tumors, and the pattern does not change upon hormone removal. The results suggest that hormonal regulation of mammary tumor growth is related to specific genetic transcripts, and loss of hormone dependence of growth may correlate with the changes in this genetic control.
Insights
Hormone removal alters gene expression in mammary tumors, causing regression. Changes in specific protein production indicate genetic modification drives tumor growth and hormone dependence.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Hormone-dependent mammary tumors regress upon hormone withdrawal.
- The underlying mechanisms of this regression are not fully understood.
Purpose of the Study:
- To investigate if mammary tumor regression is triggered by changes in genetic expression.
- To identify specific genetic alterations associated with hormone dependence.
Main Methods:
- Studied two hormone-dependent mammary carcinoma models (DMBA-induced and MTW9).
- Analyzed in vitro translation products of poly(A)+ RNAs from growing and regressing tumors.
- Compared protein profiles using electrophoresis.
- Examined tumors with autonomous growth.
Main Results:
- In vitro translation products differed between growing and regressing tumors.
- Specific protein bands (Mr 53,000, 35,000, 22,000, 20,000) decreased, while one (Mr 20,500) increased during regression.
- These changes occurred within 6 hours of hormone removal and reversed upon hormone replenishment.
- Autonomously growing tumors showed a distinct, stable translation pattern.
Conclusions:
- Hormonal regulation of mammary tumor growth involves specific genetic transcripts.
- Changes in genetic expression correlate with hormone dependence and tumor regression.
- Loss of hormone dependence may be linked to alterations in genetic control mechanisms.
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