Oncogene research: detecting & analyzing proto-oncogenes
Anti-VEGF antibody products, CEA antibody staining reagents, and more
Oncogene research comprises the identification and analysis of both proto-oncogenes and oncogenes. Proto-oncogenes are genes that frequently code for growth factors, enzymes, and cell-cycle regulators. When mutated or overexpressed, these same genes can contribute to the transformation of normal cells into cancer cells through a variety of processes including:
- Growth stimulation. Aberrant expression of growth factors can lead to excessive cell division. For example, the mitogen vascular endothelial growth factor (VEGF) is a heparin-binding growth factor specific for vascular endothelial cells that induces angiogenesis in vivo. Because analyzing VEGF family members offers key insights into cell division processes, we offer a series of anti-VEGF antibody and ELISA products to detect VEGF or VEGF-C.
- Loss of cell-cycle control. Proto-oncogenes that are overexpressed may inadvertently release cells from cell-cycle control during transitions from G1 to S phase or G2 to the M phase of mitosis. This is the case with Cyclin D1; when overexpressed this factor binds CDK4, leading to the activation of transcription factor E2F and resulting progression of the cell cycle from G1 to S phase.
- Inhibition of apoptosis. Oncogenes often block the apoptotic pathway that leads to programmed cell death; for example, overexpression of the Bcl-2 oncogene inhibits the caspase-mediated apoptotic pathway of activated B cells, which often results in B cell leukemia or lymphoma.
Oncogenes frequently serve as useful biomarkers for cancer diagnosis and prognosis and are potential therapeutic targets. For example, the oncogene carcinoembryonic antigen (CEA) is a GPI-anchored glycoprotein present in the plasma membrane. It is observed in many types of cancer cells, but is not detectable in blood samples from healthy adults, making CEA antibody staining a common method for the study of various cancers including cancers of the colon, pancreas, and breast. See examples of use from the peer-reviewed literature.
Oncogene research encompasses a spectrum of studies from biomarker discovery to drug target discovery and evaluation.
Products for oncogene research
We offer several ELISA kits and antibodies1 that can be used to analyze proto-oncogenes by western blot or immunohistochemistry2. A selection of oncogene research3 reagents is shown in the table below.
|CEA||10094A or 11021A (Clone 1B2), 11022A (Clone 2C3)||IHC||Clone 1B2 does not cross-react with CEA antisera such as nonspecific cross-reacting antigen (NCA) or NCA-2. Clone 2C3 cross-reacts with NCA, NCA-2, NFA-1, and NFA-2.|
|VEGF-C or VEGF||27756A (VEGF-C), 27171A, 27102A, 27101A (VEGF)||ELISA||Quantify human VEGF-C in serum, EDTA plasma, heparin plasma, or cell culture media. Quantify VEGF in EDTA-plasma or cell culture media using assays specific to human, rat, or mouse.|
|VEGF-A or VEGF-C||10053A, 11081A, 11085A, 18411A, 18413A, 18415A, 18420A||WB, IHC (depending on clone)||Affinity-purified VEGF Abs were raised against synthetic VEGF peptides or recombinant protein and recognize human or rat VEGF-A or VEGF-C protein. Consult product page for details.|
|Tenascin-C||27767A, 27751A||ELISA||Quantify Tenascin-C in serum, plasma, or cell culture media.|
|Tenascin-C||10335A, 10337A||WB, IHC||mAbs were raised in mouse. Consult product page for details.|
|HGF||18281A, 18131A, 18132A, 18133A, 18134A, 18135A||WB, IHC||Antibody series includes products that are species-specific (human, rat, mouse) and/or specific to HGF-alpha or beta. Consult product page for details.|
|HGF||27402A||ELISA||Quantify total human HGF (alpha and beta) in serum, EDTA-plasma, or cell culture media.|
|Bcl-1/Cyclin D-1||11011A, 11012A||WB, IHC||Antibody recognizes Cyclin D-1 and cross-reacts with Cyclin D-2. Cat.# 11012A is a biotinylated antibody.|
- Offered in partnership with IBL Co., Ltd., Japan. References listed below cite IBL or Immuno-Biological Laboratories as the kit manufacturer.
- WB, Western blot; IHC, Immunohistochemistry; ELISA, Enzyme-linked immunosorbant assay
- Products sold by Takara Bio are for Research Use Only. Not for use in Diagnostic Procedures.
Examples of oncogene research reagent usage in the literature
The studies cited below used IBL-branded antibodies for ELISA or immunostaining procedures in research on clinical samples from cancer patients or tumor-derived cell lines. The following targets were analyzed:
CEA antibody staining
- Mochizuki, K., et al. Immature squamous metaplasia (focal atypical epithelial hyperplasia) of the pancreatic duct - immunohistochemical distinction from intraductal carcinoma. Histopathology 63:343 (2013).
Immature squamous metaplasia of the pancreatic duct (ISMPD) is relatively common in healthy middle-aged and elderly individuals, as well as patients with chronic pancreatitis or pancreatic carcinoma. The presence of ISMPD can make it difficult to analyze intraductal carcinoma of the pancreas. Mochizuki and colleagues examined the levels of eight different biomarkers in ISMPD or ICP tissue samples. Anti-human CEA antibodies were used for CEA antibody staining. Differential expression was observed for ISMPD and ICP samples, with ICP samples being positive for CEA as well as five other markers.
- Timoshenko A.V., et al. Differential stimulation of VEGF-C production by adhesion/growth-regulatory galectins and plant lectins in human breast cancer cells. Anticancer Res. 30:4829 (2010).
To understand the contribution of galectins to tumor-associated lymphangiogenesis via vascular endothelial growth factor C (VEGF-C), human breast cancer cells were exposed in vitro to human lectins, using plant lectins as controls. Over-production of VEGF-C in situ promotes tumor-associated lymphangiogenesis and lymphatic metastasis of cancer. Quantitative determination of VEGF in the cell culture media was performed by a solid sandwich ELISA using Human VEGF-A and VEGF-C Assay Kits.
- Maekawa, S., et al. Correlation between lymph node metastasis and the expression of VEGF-C, VEGF-D and VEGFR-3 in T1 lung adenocarcinoma. Anticancer Res. 27:3735 (2007).
VEGF-C and VEGF-D have been implicated in lymphatic tumor spread, an important prognostic factor in patients with non-small cell lung carcinoma (NSCLC). The correlation between VEGF-C, -D, and VEGFR-3 mRNA and protein levels was examined in patients with T1 lung adenocarcinoma. Expression of VEGF-C, -D, and VEGFR-3 was analyzed using ELISA. The human VEGF-C ELISA kit was used.
- Landt, S. et al. J. Clin. Oncol. 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 24(18S) (June 20 Supplement), 2006:5016 (2006).
Serum levels of VEGF-C were measured by ELISA to evaluate prognostic relevance in cervical cancer. Significantly elevated levels of soluble VEGF-C were detected in early stage versus advanced-stage cervical cancer.
- Broutin, S. et al. Identification of soluble candidate biomarkers of therapeutic response to sunitinib in medullary thyroid carcinoma in preclinical models. Clin. Cancer Res. 17:2044 (2011).
Tenascin-C was tested as a potential marker of therapeutic response in medullary thyroid carcinoma. The Tenascin-C ELISA kit was used to assess TN-C levels in healthy versus MTC patients as well as healthy versus xenograft mice treated with the sunitinib. TN-C levels were found to decrease following sunitinib treatment.
Hepatocyte growth factor (HGF) antibody
- Tsukinoki, K, et al. Hepatocyte growth factor and c-Met immunoreactivity are associated with metastasis in high grade salivary gland carcinoma. Oncol. Reports 12:1017 (2004).
In an effort to understand the role of HGF and its receptor c-Met in salivary gland carcinoma, researchers analyzed expression patterns in clinical samples from 33 patients with high-grade salivary gland carcinomas. Anti-human HGF rabbit polyclonal antibody was used for analysis. Stromal HCF, defined as expression of HGF in fibroblasts adjacent to tumor nests, was significantly correlated with metastasis and lowered survival. Stromal HCF expression was also correlated with c-Met expression, leading the authors to suggest that HCF binds to c-Met in a paracrine fashion to promote metastasis.
- Mineta, H., et al. Cyclin D1 overexpression correlates with poor prognosis in patients with tongue squamous cell carcinoma. Oral Oncol. 36:194 (2000).
The incidence of head and neck cancers including tongue squamous cell carcinoma is increasing, prompting a need to understand factors contributing to disease incidence and progression. The authors used the Bcl-1/cyclin D-1 antibody for immunohistochemical staining of tongue squamous cell carcinoma samples from 94 patients. A positive correlation was found between Bcl-1/cyclin D-1 overexpression in tumor cells, progression of lymph node spread, and poor survival.
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