Transgenic mouse model for breast cancer: induction of breast cancer in novel oncogene HCCR-2 transgenic mice

Ko, Jesang; Shin, Seung-Soo; Oh, Young Mi; Lee, Youn Soo; Ryoo, Zae-Young; Lee, Young Han; Na, Doe Sun; Kim, Jin Woo

doi:10.1038/sj.onc.1207356

Cited by 30 publications

(44 citation statements)

References 18 publications

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“…16 We next examined whether p53 was affected in HCCRBP-1 stably transfected human HEK/293 cells since HCCR-1 induced p53 stabilization in our previous studies. 3,4 Parental HEK/293 cells or HEK/293 cells transfected with the vector alone expressed a low level of tumor suppressor protein p53 (Fig. 6a).…”

Section: Molecular Alterations In Hccrbp-1-induced Tumorigenesismentioning

confidence: 99%

“…[3][4][5][6][7] The HCCR gene is classified into the two species HCCR-1 and HCCR-2 according to molecular characteristics. The HCCR2 is an alternative splicing form of HCCR1 and corresponds to amino acids 57-360 of HCCR1.…”

mentioning

confidence: 99%

“…3 Their functional role in tumorigenesis may be a negative regulator of the p53 tumor suppressor gene. 3,4 Mice transgenic for HCCR developed breast cancers and metastasis. 4 These results suggest that HCCR represents an oncoprotein that is related to human tumorigenesis and regulation of p53.…”

mentioning

confidence: 99%

“…3,4 Mice transgenic for HCCR developed breast cancers and metastasis. 4 These results suggest that HCCR represents an oncoprotein that is related to human tumorigenesis and regulation of p53. However, it is unknown how HCCR contributes to the cellular and biochemical mechanisms of human tumorigenesis.…”

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confidence: 99%

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HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

Ha¹,

Shin²,

Lee³

et al. 2007

Intl Journal of Cancer

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Oncogene HCCR-1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. HCCR transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to human tumorigenesis. This study identified a HCCR-1-binding protein 1 (HCCRBP-1) as an HCCR binding partner by performing yeast two hybrid screening. Their endogenous interaction was further confirmed by coimmunoprecipitation experiments. These two proteins colocalized in the mitochondria. HCCRBP-1 was overexpressed in various human tumors. In addition, HCCRBP-1 alone converted NIH/3T3 cells into tumor cells in combination with no other oncogenes. HCCRBP-1 induced tumorigenesis by markedly activating PKC activities but decreasing the pro-apoptotic PKCa and PKCd isoform levels. We observed that p53 stabilization also occurred with functional impairment in HCCRBP-1-transfected 293 cells, as indicated by defective induction of p21, MDM2 and bax. Indeed, HCCRBP-1 decreased p21 promoter activity probably via p53 stabilization leading to the defective function. These results indicate that HCCRBP-1 oncogene induces p53 stabilization and thereby contributes to tumorigenesis. ' 2007 Wiley-Liss, Inc.

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Section: Molecular Alterations In Hccrbp-1-induced Tumorigenesismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

Ha¹,

Shin²,

Lee³

et al. 2007

Intl Journal of Cancer

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“…Northern and Western blot analyses and immunohistochemical studies indicate that the HCCR mRNA and protein are overexpressed in breast cancer tissues compared with the normal breast tissues (7). Mice transgenic for HCCR develop breast cancers and metastasis (9). These results indicate that HCCR is an oncoprotein that is related to breast cancer development and regulation of p53.…”

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confidence: 96%

The HCCR Oncoprotein as a Biomarker for Human Breast Cancer

Jung

Park

Lee

et al. 2005

Clinical Cancer Research

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Purpose: HCCR oncoprotein is reported to be related to tumorigenesis, including breast cancer, functioning as a negative regulator of p53. Mice transgenic for HCCR developed breast cancers. The objective of this study was to validate the HCCR oncoprotein as a candidate biomarker for breast cancer. Experimental Design: HCCR expression in breast cancer cells was analyzed by quantitative PCR, ELISA, immunohistochemistry, Western blotting, fluorescence-activated cell sorting, and confocal microscopy. Epitope areas were determined using mass spectrometry through the analysis of time-dependent tryptic fragment patterns of HCCR. HCCR expression profiles in breast cancer patient sera were analyzed, and correlations with clinicopathologic data and carbohydrate antigen 15-3 (CA15-3) levels were determined. Results: HCCR was up-regulated in breast cancer cells and tissues. The epitope regions of HCCR recognized by monoclonal antibody (BCS-1) were HFWTPK and QQTDFLDIYHAFR. According to fluorescence-activated cell sorting and confocal microscopic analysis, BCS-1 was bound to HCCR antigen on the cell surface. Serum HCCR concentrations were measured using ELISA from 299 subjects, including 129 patients with breast cancer, 24 patients with benign breast disease, and 158 normal volunteers, and comparisons were made to CA15-3. Serologic studies revealed an 86.8% sensitivity for HCCR in breast cancer, which was higher than 21.0% for CA15-3. Eighty-six of 98 (87.8%) patients with breast cancers that were negative for CA15-3 were positive for HCCR-1. A positive response rate of 83.3% was identified even at early stages for pathologic factors in breast cancer. Conclusions: The HCCR assay has an advantage over CA15-3 in diagnosing breast cancer and detecting early stages of the disease.

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HCCRBP‐3 induces tumorigenesis through direct interaction with HCCR‐1 in human cancers

Kim

Yoo

et al. 2012

Molecular Carcinogenesis

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Human cervical cancer oncogene 1, HCCR-1, is over-expressed in various human tumors and appears to serve as a negative regulator of the p53 gene. HCCR-1 transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to tumorigenesis. We identified the HCCR-1 binding protein 3 (HCCRBP-3) as a binding partner for HCCR-1. These two proteins co-localized to the mitochondria. HCCRBP-3 over-expressed in various human tumors converted normal cells into tumor cells in vitro. Nude mice injected with NIH/3T3 cells stably transfected with HCCRBP-3 also induced the tumor formation. In addition, p53 showed the functional impairment in HCCRBP-3-transfected cells as accompanied with defective induction of p21 and bax. In support of this, p21 promoter activities containing p53 responsive elements were inhibited by HCCRBP-3 in a dose-dependent manner. Therefore, our study suggests that HCCRBP-3 contributes to the HCCR-1 induced tumorigenesis by interrupting the p53 function.

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Transgenic mouse model for breast cancer: induction of breast cancer in novel oncogene HCCR-2 transgenic mice

Cited by 30 publications

References 18 publications

HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

The HCCR Oncoprotein as a Biomarker for Human Breast Cancer

HCCRBP‐3 induces tumorigenesis through direct interaction with HCCR‐1 in human cancers

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