Limits...
Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV.

Bruno RD, Rosenfield SM, Smith GH - Mol. Cancer (2013)

Bottom Line: Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3.We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.

Conclusions: These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.

Show MeSH

Related in: MedlinePlus

Relative expression of core CIS genes in NIV/Mtv-1 induced tumors and hyperplasia. The relative gene expression of Wnt1 (A), Wnt10b (B), Fgf3 (C), and Rspo2 (D) in individual Balb/c NIV tumors (red), Balb/c NIV hyperplasia (yellow), and C3hf tumors (green) are plotted as a percentage of expression in a C3H tumor (black). mRNA levels were measured by qRT-PCR and expression was calculated using the 2-ΔΔCt method. Only samples with significant expression levels above that detected in control mammary glands of Balb/c mice (Table 2) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750450&req=5

Figure 2: Relative expression of core CIS genes in NIV/Mtv-1 induced tumors and hyperplasia. The relative gene expression of Wnt1 (A), Wnt10b (B), Fgf3 (C), and Rspo2 (D) in individual Balb/c NIV tumors (red), Balb/c NIV hyperplasia (yellow), and C3hf tumors (green) are plotted as a percentage of expression in a C3H tumor (black). mRNA levels were measured by qRT-PCR and expression was calculated using the 2-ΔΔCt method. Only samples with significant expression levels above that detected in control mammary glands of Balb/c mice (Table 2) are shown.

Mentions: Total RNA was isolated from spontaneous tumors and hyperplastic outgrowths (HOGs) for analysis by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using validated primers to Wnt1, Wnt10b, Rspo2, and Fgf3 (SABiosciences/Qiagen, Valencia CA). Table 2 summarizes the samples analyzed, and in all, 5 Balb/c NIV tumors, 5 Balb/c NIV HOGs, and 6 C3Hf tumors were assayed. A C3H-MMTV mammary tumor (C3H-MT) was used as a positive control because of its high expression of all four genes. Importantly Wnt-1/10b, Rspo2, and Fgf3 are not expressed, or expressed at very low levels in normal mammary gland [8], and were not detected in pregnant mammary or liver control tissues from C3Hf and Balb/c NIV mice (Figure 2).


Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV.

Bruno RD, Rosenfield SM, Smith GH - Mol. Cancer (2013)

Relative expression of core CIS genes in NIV/Mtv-1 induced tumors and hyperplasia. The relative gene expression of Wnt1 (A), Wnt10b (B), Fgf3 (C), and Rspo2 (D) in individual Balb/c NIV tumors (red), Balb/c NIV hyperplasia (yellow), and C3hf tumors (green) are plotted as a percentage of expression in a C3H tumor (black). mRNA levels were measured by qRT-PCR and expression was calculated using the 2-ΔΔCt method. Only samples with significant expression levels above that detected in control mammary glands of Balb/c mice (Table 2) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750450&req=5

Figure 2: Relative expression of core CIS genes in NIV/Mtv-1 induced tumors and hyperplasia. The relative gene expression of Wnt1 (A), Wnt10b (B), Fgf3 (C), and Rspo2 (D) in individual Balb/c NIV tumors (red), Balb/c NIV hyperplasia (yellow), and C3hf tumors (green) are plotted as a percentage of expression in a C3H tumor (black). mRNA levels were measured by qRT-PCR and expression was calculated using the 2-ΔΔCt method. Only samples with significant expression levels above that detected in control mammary glands of Balb/c mice (Table 2) are shown.
Mentions: Total RNA was isolated from spontaneous tumors and hyperplastic outgrowths (HOGs) for analysis by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using validated primers to Wnt1, Wnt10b, Rspo2, and Fgf3 (SABiosciences/Qiagen, Valencia CA). Table 2 summarizes the samples analyzed, and in all, 5 Balb/c NIV tumors, 5 Balb/c NIV HOGs, and 6 C3Hf tumors were assayed. A C3H-MMTV mammary tumor (C3H-MT) was used as a positive control because of its high expression of all four genes. Importantly Wnt-1/10b, Rspo2, and Fgf3 are not expressed, or expressed at very low levels in normal mammary gland [8], and were not detected in pregnant mammary or liver control tissues from C3Hf and Balb/c NIV mice (Figure 2).

Bottom Line: Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3.We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.

Conclusions: These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.

Show MeSH
Related in: MedlinePlus