C-erbB

The oncogene v-erbB, unlike c-erbB, codes for a shortened form of the EGF receptor protein. Usually the binding of EGF is required to turn on the tyrosine kinase activity of the EGF receptor protein, the one coded by c-erbB. However, the tyrosine kinase activity of the receptor derived from v-erbB is switched on permanently, even in the absence of EGF. The uncontrolled grqwth characteristic of cancer cells results. 

Troncone G, Panico L, Vetrani A, et al. c-erbB-2 expression in FNAB smears and matched surgical specimens of breast cancer. Diagn. Cytopathol. 1996 14 135-139. 

Preliminary evidence suggest that c-erbB-2 may also be a prognostic marker for other cancers such as gastric (Y2), ovarian (S7), cervical (K5), and nonsmall cell carcinoma of the lung (K3). Thus, c-erbB-2 has the potential to be a prognostic marker for many different types of adenocarcinomas. 

As with c-erbB, overexpression of the suppressor p53 gene product has been found in different cancers (H3). Initially, it was believed that the detection of p53 protein in tumors meant the presence of a mutant gene product. However, we now know that normal p53 protein can be overexpressed in response to certain stimuli and stabilized by interaction with both cellular and viral proteins (H3). Irrespective of the mechanism giving rise to elevated protein levels, overexpression of p53 has been shown to be a prognostic marker in both breast and colorectal cancers (D8). In some studies, the presence of high levels of p53 has been shown to be a prognostic marker in axillary node-negative breast cancer patients (H3). 

G6. Gullick, W. J., Love, S. B., Wright, C., Barnes, D. M., Gusterson, B., Harris, A. L., and Altman, D. G., C-erbb-2 protein overexpression in breast cancer is a risk factor with involved and uninvolved lymph nodes. Br. J. Cancer 63, 434-438 (1991). 

K5. Kihana, T., Tsuda, H., Teshima, S., Nomoto, K., Tsugane, S., Sonoda, T., Matsuura, S., and Hirohashi, S., Prognostic significance of the overexpression of c-erbB-2 protein in adenocarcinoma of the uterine cervix. Cancer (Philadelphia) 73, 148-153 (1994). 

Raziuddin A, Court D, Sarkar FH, Liu YL, Kung H, Raziuddin R (1997) A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor tissues mediates NF-kappaB DNA binding activity. / Biol Chem 272(25) 15715-15720... 

Nagata Y, et al. Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts. J Immunol 1997 159 1336. 

Giatromanolaki A, Koukourakis MI, O Byrne K, et al. Non-small cell lung cancer c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. Anticancer Res 1996 16 3819-3825. 

C-erbB-2 oncoprotein Nonspecific marker, more frequent in breast carcinoma... 

Several cancer cell types are characterized by expressing a truncated EGF receptor. The related viral oncogene, V-er B, also encodes a truncated receptor which lacks most of the extracellular domain (the EGF receptor is also known as C-erbB). Mutant receptors that display inappropriate constitutive activity can lead to cellular transformation, due to the continuous generation of mitogenic signal. 

Epidermal growth factor, EGF Transforming growth factor-a, TGF-a ca 6 kD, EGF und TGF-a are up to 40 % identical Receptor tyrosine kinase. EGF-R is a produkt of the c-erbB proto-oncogene... 

Tauroacidins A (194) and B (195) from an Okinawan sponge Hymeniacidon sp. exhibit inhibitory activity against EGF receptor kinase and c-erbB-2 kinase (IC50 20 pg/ml each) [155]. 

Spongiacidins A (197) and B (198), azepine-type bromopyrrole alkaloids from Hymeniacidon which are geometrical isomers of hymenialdisine (171), inhibit c-erbB-2 kinase (IC50 9.0 and 8.5 pg/ml) and cyclin dependent kinase 4 (IC50 32 and 12 pg/ml) [157],... 

HER-2/nen gene was first discovered as a transforming oncogene in a series of ethyl nitrosourea-induced rat neuroblastomas, where it was called neu (Schecter et al., 1984). Approximately 15 years ago, this oncogene was isolated independently by two separate groups, which named it HER-2 (Coussens et al., 1985) and c-erbB-2 (Semba et al., 1985), respectively. Further evidence revealed that the two genes were the same (Schechter et al., 1985), and it was renamed HER-2Ineu. 

FIGURE 12.3. Immunostained HER-2 protein in invasive breast carcinoma without antigen retrieval. Note homogeneous, predominantly membranous staining some cytoplasmic staining is also present. Monoclonal anti-c-erbB-2 antibody (diluted 1 200) (Triton, Almeda, CA) was used as the primary antibody. Courtesy of Jun Horiguchi. 

Battifora, H., Gaffey, M., Esteban, J., Mehta, R, Bailey, A., Faucett, C., and Niland, J. 1991. Immunohistochemical assay of neu/c-erbB-2 oncogene product in paraffin-embedded tissues in early breast cancer Retrospective follow-up study of 245 stage I and II cases. Mod. Pathol. 4 466-414. 

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