Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 1Date:7 February 2008
Reviewer: Onno Kranenburg
Reviewer's report:
In the present manuscript Patek et al have examined the role of the Kras4A
splice variant in intestinal tumor development driven by heterozygous loss of
APC. This group previously reported that the 4A/4B ratio is altered in favor of 4B
in CRC. Based on this observation they formed the hypothesis that alteration of
the 4A/4B ratio may affect tumor formation. The study is based on the use of the
tmï##4A mouse that lacks the 4A splice variant and that was previously
generated in the same lab. By crossing these mice with the well known APC-Min
mouse they show that loss of 4A has no effect on tumor development and
survival.
The paper is well written, the data are clear and convey a simple message that is
well explained.
I have one suggestion for improving the current manuscript. Given the
differences in 4A and 4B with respect to stimulation of cell proliferation, motility,
invasion and apoptosis induction it would be interesting to see whether the
proliferation-apoptosis ratio is altered in APC-Min versus APC-Min/tmdelta4A
tumors by immunohistochemistry for markers of apoptosis (e.g. activated
caspase 3) and proliferation (e.g. Ki67). Likewise, it would be informative to
analyze tissue sections by histochemistry to assess whether the 2 types of
tumors differ in their ability to invade the underlying submucosa.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 1Date:7 February 2008
Reviewer: Onno Kranenburg
Reviewer's report:
In the present manuscript Patek et al have examined the role of the Kras4A
splice variant in intestinal tumor development driven by heterozygous loss of
APC. This group previously reported that the 4A/4B ratio is altered in favor of 4B
in CRC. Based on this observation they formed the hypothesis that alteration of
the 4A/4B ratio may affect tumor formation. The study is based on the use of the
tmï##4A mouse that lacks the 4A splice variant and that was previously
generated in the same lab. By crossing these mice with the well known APC-Min
mouse they show that loss of 4A has no effect on tumor development and
survival.
The paper is well written, the data are clear and convey a simple message that is
well explained.
I have one suggestion for improving the current manuscript. Given the
differences in 4A and 4B with respect to stimulation of cell proliferation, motility,
invasion and apoptosis induction it would be interesting to see whether the
proliferation-apoptosis ratio is altered in APC-Min versus APC-Min/tmdelta4A
tumors by immunohistochemistry for markers of apoptosis (e.g. activated
caspase 3) and proliferation (e.g. Ki67). Likewise, it would be informative to
analyze tissue sections by histochemistry to assess whether the 2 types of
tumors differ in their ability to invade the underlying submucosa.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 1Date:7 February 2008
Reviewer: Onno Kranenburg
Reviewer's report:
In the present manuscript Patek et al have examined the role of the Kras4A
splice variant in intestinal tumor development driven by heterozygous loss of
APC. This group previously reported that the 4A/4B ratio is altered in favor of 4B
in CRC. Based on this observation they formed the hypothesis that alteration of
the 4A/4B ratio may affect tumor formation. The study is based on the use of the
tmï##4A mouse that lacks the 4A splice variant and that was previously
generated in the same lab. By crossing these mice with the well known APC-Min
mouse they show that loss of 4A has no effect on tumor development and
survival.
The paper is well written, the data are clear and convey a simple message that is
well explained.
I have one suggestion for improving the current manuscript. Given the
differences in 4A and 4B with respect to stimulation of cell proliferation, motility,
invasion and apoptosis induction it would be interesting to see whether the
proliferation-apoptosis ratio is altered in APC-Min versus APC-Min/tmdelta4A
tumors by immunohistochemistry for markers of apoptosis (e.g. activated
caspase 3) and proliferation (e.g. Ki67). Likewise, it would be informative to
analyze tissue sections by histochemistry to assess whether the 2 types of
tumors differ in their ability to invade the underlying submucosa.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
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