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Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer

Lawson, James S; Tran, Dinh D; Ford, Caroline LU and Rawlinson, William D (2004) In Breast Cancer Research and Treatment 87(1). p.13-17
Abstract
Mouse mammary tumor virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible laboratory inbred mice. The carcinogenic characteristics of this virus are enhanced by estrogen and other steroid hormones. MMTV-like envelope gene sequences, with 95% homology to MMTV have been identified in approximately 40% of breast cancers in US, Australian and Argentinian women. The presence of such sequences indicates the presence of a replication competent MMTV-like virus in human breast tumors. Whether an MMTV-like virus contributes to human breast cancer remains to be demonstrated. Non-statistically significant differences in p53 expression between MMTV-like positive and negative human breast cancers have... (More)
Mouse mammary tumor virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible laboratory inbred mice. The carcinogenic characteristics of this virus are enhanced by estrogen and other steroid hormones. MMTV-like envelope gene sequences, with 95% homology to MMTV have been identified in approximately 40% of breast cancers in US, Australian and Argentinian women. The presence of such sequences indicates the presence of a replication competent MMTV-like virus in human breast tumors. Whether an MMTV-like virus contributes to human breast cancer remains to be demonstrated. Non-statistically significant differences in p53 expression between MMTV-like positive and negative human breast cancers have previously been observed. As high p53 protein expression is associated with aggressive breast carcinogenesis we sought to determine if there were associations between the presence of MMTV-like gene sequences and elevated p53 expression in both invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS). We also investigated the expression of other biomarkers which are commonly associated with human breast cancer. These included estrogen receptor, progesterone receptor, Ki67, Cyclin D1, Bcl-2 and HER-2. Using polymerase chain reaction (PCR) analyses, MMTV-like envelope gene sequences were detected in 15 (75%) of 20 IDC specimens and 5 (23%) of 22 DCIS specimens. The average percentage of p53 positive cells in MMTV-like positive IDC specimens was 69% as compared to 44% in MMTV-like negative specimens (p for difference = 0.067). The average percentage of p53 positive cells in MMTV-like positive DCIS specimens was 93% as compared to 35% in MMTV-like negative specimens (numbers too few for statistical analysis). There was an increased intensity of p53 expression in IDC and DCIS specimens that were MMTV-like positive compared to those that were MMTV-like negative. There were no statistically significant differences in age, grade, and percentage of average positive cells for ERa, PR, Ki67, cyclin D1, Bcl-2, and HER-2, between MMTV-like positive and negative breast cancer specimens. Although these observations do not provide evidence of causality, they are consistent with a role for MMTV-like viruses in some human breast cancers. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research and Treatment
volume
87
issue
1
pages
13 - 17
publisher
Springer
external identifiers
  • pmid:15377846
  • scopus:4544239234
ISSN
1573-7217
DOI
10.1023/B:BREA.0000041573.09142.00
language
English
LU publication?
no
id
03e8cf81-bcd4-4beb-b65f-c58fc9323262 (old id 1130025)
date added to LUP
2008-06-16 14:38:57
date last changed
2017-01-01 07:23:36
@article{03e8cf81-bcd4-4beb-b65f-c58fc9323262,
  abstract     = {Mouse mammary tumor virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible laboratory inbred mice. The carcinogenic characteristics of this virus are enhanced by estrogen and other steroid hormones. MMTV-like envelope gene sequences, with 95% homology to MMTV have been identified in approximately 40% of breast cancers in US, Australian and Argentinian women. The presence of such sequences indicates the presence of a replication competent MMTV-like virus in human breast tumors. Whether an MMTV-like virus contributes to human breast cancer remains to be demonstrated. Non-statistically significant differences in p53 expression between MMTV-like positive and negative human breast cancers have previously been observed. As high p53 protein expression is associated with aggressive breast carcinogenesis we sought to determine if there were associations between the presence of MMTV-like gene sequences and elevated p53 expression in both invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS). We also investigated the expression of other biomarkers which are commonly associated with human breast cancer. These included estrogen receptor, progesterone receptor, Ki67, Cyclin D1, Bcl-2 and HER-2. Using polymerase chain reaction (PCR) analyses, MMTV-like envelope gene sequences were detected in 15 (75%) of 20 IDC specimens and 5 (23%) of 22 DCIS specimens. The average percentage of p53 positive cells in MMTV-like positive IDC specimens was 69% as compared to 44% in MMTV-like negative specimens (p for difference = 0.067). The average percentage of p53 positive cells in MMTV-like positive DCIS specimens was 93% as compared to 35% in MMTV-like negative specimens (numbers too few for statistical analysis). There was an increased intensity of p53 expression in IDC and DCIS specimens that were MMTV-like positive compared to those that were MMTV-like negative. There were no statistically significant differences in age, grade, and percentage of average positive cells for ERa, PR, Ki67, cyclin D1, Bcl-2, and HER-2, between MMTV-like positive and negative breast cancer specimens. Although these observations do not provide evidence of causality, they are consistent with a role for MMTV-like viruses in some human breast cancers.},
  author       = {Lawson, James S and Tran, Dinh D and Ford, Caroline and Rawlinson, William D},
  issn         = {1573-7217},
  language     = {eng},
  number       = {1},
  pages        = {13--17},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer},
  url          = {http://dx.doi.org/10.1023/B:BREA.0000041573.09142.00},
  volume       = {87},
  year         = {2004},
}